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Titolo
Identificazione di sistemi di rilascio ottimali per i Nucleic Acid Based Drugs e studio dei meccanismi di azione in alcuni modelli di patologie umane infiammatorie e tumorali
Coordinatore: Mario Grassi
Sommario
Per il carcinoma epatocellulare, l’adenocarcinoma prostatico, la restenosi coronarica, l’aneurisma dell’aorta addominale, le patologie infiammatorie croniche dell’intestino e del polmone, tutte patologie ad ampia diffusione, è urgente un significativo miglioramento dell’efficacia degli approcci terapeutici disponibili. L’uso dei farmaci basati sugli acidi nucleici (NABD), una nuova ed emergente classe di molecole, è considerato molto promettente. Tuttavia, una limitazione all’uso dei NABD dipende dalla mancanza di sistemi di rilascio ottimali in grado di minimizzare la degradazione dei NABD nei fluidi biologici e di permetterne un’azione mirata ai soli tessuti malati.
Scopo di questo progetto è di sviluppare nuovi sistemi di rilascio per i NABD, adeguati alle patologie considerate. Il problema verrà affrontato dal punto di vista ingegneristico, ma anche chimico-farmacetico e bio-medico. Parteciperanno al progetto nove gruppi Universitari con il supporto di diciassette gruppi di ricerca non universitari.
Unità di ricerca
Unità | Responsabile | Attività |
01. UNITS | Mario Grassi | Read More
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02. UNISA | Gaetano Lamberti | Read More
Le attività principali del progetto di ricerca consisteranno nel:
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03. UNIPV | Piersandro Pallavicini | Read More
Per individuare un’efficace terapia per il carcinoma epatocellulare, studieremo il rilascio di NABD, selezionati dall’Unità 01, per mezzo di nanovettori basati su nanoparticelle d’oro non simmetriche (asymmetric branched nanoparticles, ABN) e su nanoparticelle sferiche di magnetite (MNP). |
04. UNINA | Stefano Guido | Read More
L’attività sarà focalizzata sullo studio dell’interazione tra le cellule del sangue umano, in particolare dei globuli rossi, sia con le pareti dei vasi che con le micro/nano particelle sviluppate dalle altre Unità per il trasporto e il rilascio dei NABD. |
05. CNR NA | Domenico Larobina | Read More
L’obbiettivo è quello di fornire informazioni strutturali sui sistemi impiegati nel rilascio dei NABD proposti dalle altre Unità coinvolte nel progetto. A tal fine verranno utilizzate sia tecniche spettroscopiche che meccaniche. Tale caratterizzazione costituisce un indispensabile supporto conoscitivo necessario alla messa a punto dei dispositivi in grado di rilasciare i NABD. |
06. UNIPA1 | Gennara Cavallaro | Read More
Progetteremo sistemi di rilascio per i NABD utilizzabili nelle condizioni patologiche proposte dalle Unità 01, 02, 08; in particolare, valuteremo:
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07. UNIPA2 | Valerio Brucato | Read More
Prepareremo scaffolds polimerici (PLLA e/o mix PLLA/PLA) pre-angiogenizzati, come da brevetto proprietario, ed effettueremo test “in vitro” sul rilascio di NABD. |
08. UNIFG | Sante Di Gioia | Read More
Al fine di trovare nuovi approcci terapeutici dell’asma grave, proponiamo di usare NABD diretti contro GM-CSF, HMGB1, e TGF-ß1. In collaborazione con l’Unità 01 verranno selezionati i NABD appropriati; con il supporto Unità 02, 05 e 06 verranno sviluppati adeguati sistemi di rilascio.
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09. POLIMI | Davide Manca | Read More
Il nostro contributo consiste in un servizio di modellazione matematica per le Unità del presente progetto. La modellazione riguarderà due argomenti diversi:
Per entrambi gli obiettivi, di particolare utilità sarà il modello sviluppato dall’Unità 07 |
Prodotti della ricerca
Articoli pubblicati su riviste internazionali
Read More2014
Halib, N; Amin, M. C. I. Mohd; Ahmad,; Abrami, Michela; Fiorentino, Simona; Farra, Rossella; Grassi, Gabriele; Musiani, F; LAPASIN, Romano; Grassi, Mario
Topological characterization of a bacterial cellulose–acrylic acid polymeric matrix Journal Article
In: European Journal of Pharmaceutical Sciences, vol. 62, pp. 326-333, 2014.
Abstract | Links | BibTeX | Tags:
@article{Halib2014,
title = {Topological characterization of a bacterial cellulose\textendashacrylic acid polymeric matrix},
author = {N Halib and M.C.I. Mohd Amin and . Ahmad and Michela Abrami and Simona Fiorentino and Rossella Farra and Gabriele Grassi and F Musiani and Romano LAPASIN and Mario Grassi},
url = {http://www.sciencedirect.com/science/article/pii/S0928098714002644},
doi = {10.1016/j.ejps.2014.06.004},
year = {2014},
date = {2014-10-01},
journal = {European Journal of Pharmaceutical Sciences},
volume = {62},
pages = {326-333},
abstract = {This paper focuses on the micro- and nano-topological organization of a hydrogel, constituted by a
mixture of bacterial cellulose and acrylic acid, and intended for biomedical applications. The presence
of acrylic acid promotes the formation of two interpenetrated continuous phases: the primary ‘‘pores
phase’’ (PP) containing only water and the secondary ‘‘polymeric network phase’’ (PNP) constituted by
the polymeric network swollen by the water. Low field Nuclear Magnetic Resonance (LF NMR), rheology,
Scanning Electron Microscopy (SEM) and release tests were used to determine the characteristics of the
two phases. In particular, we found that this system is a strong hydrogel constituted by 81% (v/v) of PP
phase the remaining part being occupied by the PNP phase. Pores diameters span in the range
10\textendash100 lm, the majority of them (85%) falling in the range 30\textendash90 lm. The high PP phase tortuosity indicates
that big pores are not directly connected to each other, but their connection is realized by a series of
interconnected small pores that rend the drug path tortuous. The PNP is characterized by a polymer
volume fraction around 0.73 while mesh size is around 3 nm.
The theoretical interpretation of the experimental data coming from the techniques panel adopted,
yielded to the micro- and nano-organization of our hydrogel
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
mixture of bacterial cellulose and acrylic acid, and intended for biomedical applications. The presence
of acrylic acid promotes the formation of two interpenetrated continuous phases: the primary ‘‘pores
phase’’ (PP) containing only water and the secondary ‘‘polymeric network phase’’ (PNP) constituted by
the polymeric network swollen by the water. Low field Nuclear Magnetic Resonance (LF NMR), rheology,
Scanning Electron Microscopy (SEM) and release tests were used to determine the characteristics of the
two phases. In particular, we found that this system is a strong hydrogel constituted by 81% (v/v) of PP
phase the remaining part being occupied by the PNP phase. Pores diameters span in the range
10–100 lm, the majority of them (85%) falling in the range 30–90 lm. The high PP phase tortuosity indicates
that big pores are not directly connected to each other, but their connection is realized by a series of
interconnected small pores that rend the drug path tortuous. The PNP is characterized by a polymer
volume fraction around 0.73 while mesh size is around 3 nm.
The theoretical interpretation of the experimental data coming from the techniques panel adopted,
yielded to the micro- and nano-organization of our hydrogel
Dapas, Barbara; Dall'Acqua, Stefano; Bulla, Roberta; Agostinis, Chiara; Perissutti, Beatrice; Invernizzi, Sergio; Grassi, Gabriele; Voinovich, Dario
In: Phytomedicine, vol. 21, no 11, pp. 1406–1410, 2014.
Abstract | Links | BibTeX | Tags: Cytokines, Echinacea angustifolia root standardized extract (Polinacea®), Herbal syrup; Immune stimulating activity, Human gene expression
@article{Dapas2014b,
title = {Immunomodulation mediated by a herbal syrup containing a standardized Echinacea root extract: A pilot study in healthy human subjects on cytokine gene expression},
author = {Barbara Dapas and Stefano Dall'Acqua and Roberta Bulla and Chiara Agostinis and Beatrice Perissutti and Sergio Invernizzi and Gabriele Grassi and Dario Voinovich },
url = {http://www.sciencedirect.com/science/article/pii/S0944711314002219},
doi = {10.1016/j.phymed.2014.04.034},
year = {2014},
date = {2014-09-25},
journal = {Phytomedicine},
volume = {21},
number = {11},
pages = {1406\textendash1410},
abstract = {n this study, the immunomodulatory effect of a triply standardized Echinacea angustifolia root extract (Polinacea®) was evaluated in 10 healthy subjects. Ten ml of syrup containing one hundred mg of extract (corresponding to 4.7 mg of Echinacoside and 8.0 mg of a high molecular weight-20,000 Da- polysaccharide) were administered as a herbal syrup once a day for one month. The immunomodulatory effect was evaluated before and after herbal syrup administration evaluating the expression levels of the cytokines IL-2, IL-8, IL-6 and TNF-α. Cytokine expression was studied in lympho-monocytes and in plasma samples measuring the mRNA and protein levels, respectively. The results were analysed by ANOVA and non-parametric Friedman rank sum tests; when possible it was adopted a pair-wise comparisons at different post-treatment times, using the paired t-tests with Holm correction. The correlation between the variations of cytokine plasma levels and the respective mRNA was carried out using a linear regression model.
In lympho-monocytes our data indicate the up-regulation of the mRNA levels of IL-2 and IL-8 and the down regulation of the mRNA levels of the pro-inflammatory cytokines TNF-α and IL6. The differential regulation was maximal after 14 days of treatment. IL-2 up-regulation and IL-6 down-regulation were also confirmed at the protein level in plasma. Finally, the up-regulation of the mRNA of IL-2/IL-8 and the down-regulation of IL-6 positively correlated with the protein levels detected in the plasma.
In conclusion, this pilot study suggests a relevant role for the standardized Echinacea angustifolia root extract in the control of cytokine expression. This first demonstration of the immuno-modulating activity of Echinacea angustifolia root extract in the healthy subject, supports at least in part the common use of such products as health promoting supplement.},
keywords = {Cytokines, Echinacea angustifolia root standardized extract (Polinacea®), Herbal syrup; Immune stimulating activity, Human gene expression},
pubstate = {published},
tppubtype = {article}
}
In lympho-monocytes our data indicate the up-regulation of the mRNA levels of IL-2 and IL-8 and the down regulation of the mRNA levels of the pro-inflammatory cytokines TNF-α and IL6. The differential regulation was maximal after 14 days of treatment. IL-2 up-regulation and IL-6 down-regulation were also confirmed at the protein level in plasma. Finally, the up-regulation of the mRNA of IL-2/IL-8 and the down-regulation of IL-6 positively correlated with the protein levels detected in the plasma.
In conclusion, this pilot study suggests a relevant role for the standardized Echinacea angustifolia root extract in the control of cytokine expression. This first demonstration of the immuno-modulating activity of Echinacea angustifolia root extract in the healthy subject, supports at least in part the common use of such products as health promoting supplement.
Tomaiuolo, Giovanna
Biomechanical properties of red blood cells in health and disease towards microfluidics Journal Article
In: Biomicrofluidics, vol. 8, no 051501, 2014.
Abstract | Links | BibTeX | Tags:
@article{Tomaiuolo2014,
title = {Biomechanical properties of red blood cells in health and disease towards microfluidics},
author = {Giovanna Tomaiuolo},
url = {http://scitation.aip.org/content/aip/journal/bmf/8/5/10.1063/1.4895755},
doi = {10.1063/1.4895755},
year = {2014},
date = {2014-09-17},
journal = {Biomicrofluidics},
volume = {8},
number = {051501},
abstract = {Red blood cells (RBCs) possess a unique capacity for undergoing cellular deformation to navigate across various human microcirculation vessels, enabling them to pass through capillaries that are smaller than their diameter and to carry out their role as gas carriers between blood and tissues. Since there is growing evidence that red blood cell deformability is impaired in some pathological conditions, measurement of RBC deformability has been the focus of numerous studies over the past decades. Nevertheless, reports on healthy and pathological RBCs are currently limited and, in many cases, are not expressed in terms of well-defined cell membrane parameters such as elasticity and viscosity. Hence, it is often difficult to integrate these results into the basic understanding of RBC behaviour, as well as into clinical applications. The aim of this review is to summarize currently available reports on RBC deformability and to highlight its association with various human diseases such as hereditary disorders (e.g., spherocytosis, elliptocytosis, ovalocytosis, and stomatocytosis), metabolic disorders (e.g., diabetes, hypercholesterolemia, obesity), adenosine triphosphate-induced membrane changes, oxidative stress, and paroxysmal nocturnal hemoglobinuria. Microfluidic techniques have been identified as the key to develop state-of-the-art dynamic experimental models for elucidating the significance of RBC membrane alterations in pathological conditions and the role that such alterations play in the microvasculature flow dynamics.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Dalmoro, Annalisa; Barba, Anna Angela; Lamberti, Marina; Mazzeo, Mina; Venditto, Vincenzo; Lamberti, Gaetano
Random l-lactide/$epsilon$-caprolactone copolymers as drug delivery materials Journal Article
In: Journal of Materials Science, vol. 49, no 17, pp. 5986–5996, 2014, ISSN: 0022-2461.
Abstract | Links | BibTeX | Tags:
@article{Dalmoro2014a,
title = {Random l-lactide/$epsilon$-caprolactone copolymers as drug delivery materials},
author = { Annalisa Dalmoro and Anna Angela Barba and Marina Lamberti and Mina Mazzeo and Vincenzo Venditto and Gaetano Lamberti},
url = {http://link.springer.com/10.1007/s10853-014-8317-x},
doi = {10.1007/s10853-014-8317-x},
issn = {0022-2461},
year = {2014},
date = {2014-09-01},
journal = {Journal of Materials Science},
volume = {49},
number = {17},
pages = {5986--5996},
publisher = {Springer US},
abstract = {In this work, the degradation phenomena and the release kinetics of an active molecule from matrices systems made of random copolymers of $epsilon$-caprolactone (CL) and l-lactide (LA) were investigated by exposing the matrices, shaped as thin films, to simulated physiological environments. $alpha$-tocopherol was incorporated into the films as hydrophobic model molecule with the aim to investigate both its release pattern and its effect on erosion phenomena. In particular, the films have been kept at controlled conditions (temperature, stirring, pH) and they were characterized in terms of weight loss, water uptake, thermal properties, and change of number average molecular weight, in order to explain the molecule release kinetics and the degradation pathways of the copolymers. The main findings of this study are that the erosion phenomena take place significantly only when a critical value of the molecular mass was obtained in the sample; that the presence of the drug stabilizes the matrix and it decreases the rate of molecular mass decrease; and that crystallinity, reducing the chain mobility, causes lower erosion rates.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Dapas, Barbara; Grassi, Mario; Grassi, Gabriele
Can TIE-2 expressing monocytes represent a novel marker for hepatocellular carcinoma? Journal Article
In: Hepatobiliary Surgery and Nutrition, vol. 3, no 4, pp. 175-178, 2014.
Abstract | Links | BibTeX | Tags: Hepatocellular carcinoma (HCC), markers, TIE-2-expressing monocytes (TEMs), tyrosine kinase with Ig and endothelial growth factor (EGF) homology domains 2 (TIE2)
@article{Dapas2014,
title = {Can TIE-2 expressing monocytes represent a novel marker for hepatocellular carcinoma?},
author = {Barbara Dapas and Mario Grassi and Gabriele Grassi},
url = {http://www.thehbsn.org/article/view/4244/5164},
doi = {10.3978/j.issn.2304-3881.2014.07.07},
year = {2014},
date = {2014-08-01},
journal = {Hepatobiliary Surgery and Nutrition},
volume = {3},
number = {4},
pages = {175-178},
abstract = {Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is a global health problem representing the sixth most common cancer and the third cause of cancer related death worldwide. The number of deaths per year in HCC is comparable to the incidence number, underlying the aggressive behavior of HCC and the modest efficacy of available curative treatments. Effective HCC treatment is problematic also due to the lack of early and specific diagnostic markers. In this regard, particular interest has been put on the tyrosine kinase with Ig and endothelial growth factor (EGF) homology domains 2 (TIE2), a receptor of angiopoietins, predominantly present on endothelial cells but also observed on monocytes [TIE-2-expressing monocytes (TEMs)]. Recently, a work by Matsubara et al. showed that the amount of circulating TEMs is higher in hepatitis virus C (HCV)/HCC patients compared to HCV patients or healthy subjects. Additionally the authors showed that TEMs have a diagnostic potential for HCC. Whereas the molecular mechanisms responsible for this observation remain elusive and further studies are necessary to confirm this finding, the work of Matsubara et al. may contribute to the identification of a novel HCC prognostic and diagnostic marker.},
keywords = {Hepatocellular carcinoma (HCC), markers, TIE-2-expressing monocytes (TEMs), tyrosine kinase with Ig and endothelial growth factor (EGF) homology domains 2 (TIE2)},
pubstate = {published},
tppubtype = {article}
}
Cont, Renzo Del; Abrami, Michela; Hasa, Dritan; Perissutti, Beatrice; Voinovich, Dario; Barba, Anna Angela; Lamberti, Gaetano; Grassi, Gabriele; Colombo, Italo; Manca, Davide; Grassi, Mario
A physiologically oriented mathematical model for the description of in vivo drug release and absorption Journal Article
In: ADMET & DMPK, vol. 2, no 2, pp. 80–97, 2014, ISSN: 1848-7718.
Abstract | Links | BibTeX | Tags: In silico, Pharmacokinetics
@article{del2014physiologically,
title = {A physiologically oriented mathematical model for the description of in vivo drug release and absorption},
author = {Renzo {Del Cont} and Michela Abrami and Dritan Hasa and Beatrice Perissutti and Dario Voinovich and Anna Angela Barba and Gaetano Lamberti and Gabriele Grassi and Italo Colombo and Davide Manca and Mario Grassi},
url = {http://pub.iapchem.org/ojs/index.php/admet/article/view/34},
doi = {10.5599/admet.2.2.34},
issn = {1848-7718},
year = {2014},
date = {2014-07-01},
journal = {ADMET \& DMPK},
volume = {2},
number = {2},
pages = {80--97},
abstract = {This paper focuses on a physiologically-oriented mathematical model aimed at studying the in vivo drug release, absorption, distribution, metabolism and elimination (ADME). To this purpose, the model accounts for drug delivery from an ensemble of non-eroding poly-disperse polymeric particles and the subsequent ADME processes. The model outcomes are studied with reference to three widely used drugs: theophylline, temazepam and nimesulide. One of the most important results of this study is the quantitative evaluation of the interplay between the release kinetics and the subsequent ADME processes. Indeed, it is usually assumed that in vivo drug release coincides with in vitro so that the effect exerted by the ADME processes is neglected. In addition, the proposed model may be an important tool for the design of delivery systems since, through proper changes, it could also account for different oral delivery systems.},
keywords = {In silico, Pharmacokinetics},
pubstate = {published},
tppubtype = {article}
}
Grassi, Mario; Grassi, Gabriele
Application of mathematical modeling in sustained release delivery systems. Journal Article
In: Expert Opinion on Drug Delivery, vol. 11, no 8, pp. 1299-1321, 2014.
Abstract | Links | BibTeX | Tags:
@article{Grassi2014,
title = {Application of mathematical modeling in sustained release delivery systems.},
author = {Mario Grassi and Gabriele Grassi},
url = {http://www.tandfonline.com/doi/abs/10.1517/17425247.2014.924497?journalCode=iedd20},
doi = {10.1517/17425247.2014.924497},
year = {2014},
date = {2014-06-17},
journal = {Expert Opinion on Drug Delivery},
volume = {11},
number = {8},
pages = {1299-1321},
abstract = {Introduction: This review, starting with the concept of mathematical model, is aimed at the physical and mathematical description of the most important mechanisms ruling drug delivery. Indeed, their combination allows building up powerful mathematical models able to describe how different delivery systems work. This is essential for their reliable designing.
Areas covered: The mechanisms retained fundamental for drug delivery are drug diffusion, delivery system swelling, erosion, drug dissolution with possible re-crystallisation (this is the case of amorphous and nano-crystalline drugs, for example), initial drug distribution inside the delivery system, delivery system geometry and delivery system polydisperisty, this being the case of multiparticulate systems. As these mechanisms do not simultaneously play the same role in the various delivery systems, model building require enucleating the really important mechanisms for the specified delivery system.
Expert opinion: In the light of the most recent findings, we believe that mathematical modelling has a tremendous potentiality for the pharmaceutical field although industrial world seems still a little diffident. Nevertheless, we believe that mathematical modelling will be more and more important in the next future for the rapid advent of personalised medicine that is intended to specifically treat each patient instead of the “average” patient.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Areas covered: The mechanisms retained fundamental for drug delivery are drug diffusion, delivery system swelling, erosion, drug dissolution with possible re-crystallisation (this is the case of amorphous and nano-crystalline drugs, for example), initial drug distribution inside the delivery system, delivery system geometry and delivery system polydisperisty, this being the case of multiparticulate systems. As these mechanisms do not simultaneously play the same role in the various delivery systems, model building require enucleating the really important mechanisms for the specified delivery system.
Expert opinion: In the light of the most recent findings, we believe that mathematical modelling has a tremendous potentiality for the pharmaceutical field although industrial world seems still a little diffident. Nevertheless, we believe that mathematical modelling will be more and more important in the next future for the rapid advent of personalised medicine that is intended to specifically treat each patient instead of the “average” patient.
Craparo, Emanuela Fabiola; Sardo, Carla; Serio, Rosa; Zizzo, Maria Grazia; Bondì, Maria Luisa; Giammona, Gaetano; Cavallaro, Gennara
Galactosylated polymeric carriers for liver targeting of sorafenib Journal Article
In: International Journal of Pharmaceutics, vol. 466, no 1-2, pp. 172–180, 2014.
Abstract | Links | BibTeX | Tags: Active targeting, Galactosylation, Hepatic cell-targeted carriers, Polymeric micelles
@article{Craparo2014,
title = {Galactosylated polymeric carriers for liver targeting of sorafenib},
author = {Emanuela Fabiola Craparo and Carla Sardo and Rosa Serio and Maria Grazia Zizzo and Maria Luisa Bond\`{i} and Gaetano Giammona and Gennara Cavallaro},
url = {http://www.sciencedirect.com/science/article/pii/S0378517314001458},
doi = {10.1016/j.ijpharm.2014.02.047},
year = {2014},
date = {2014-05-15},
journal = {International Journal of Pharmaceutics},
volume = {466},
number = {1-2},
pages = {172\textendash180},
abstract = {In this paper, we describe the preparation of liver-targeted polymeric micelles potentially able to carry sorafenib to hepatocytes for treatment of hepatocarcinoma (HCC), exploiting the presence of carbohydrate receptors, ASGPR. These micelles were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-d,l-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, leading to PHEA-EDA-PLA-GAL copolymer. Liver-targeted sorafenib-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometer size and slightly positive zeta potential. Biodistribution studies on mice demonstrated, after oral administration of sorafenib loaded PHEA-EDA-PLA-GAL micelles, the preferential sorafenib accumulation into the liver. This finding raises hope in terms of future drug delivery strategy of sorafenib-loaded micelles targeted to the liver for the HCC treatment.},
keywords = {Active targeting, Galactosylation, Hepatic cell-targeted carriers, Polymeric micelles},
pubstate = {published},
tppubtype = {article}
}
Cavallaro, Gennara; Licciardi, Mariano; Amato, Giovanni; Sardo, Carla; Giammona, Gaetano; Farra, Rossella; Dapas, Barbara; Grassi, Mario; Grassi, Gabriele
Synthesis and characterization of polyaspartamide copolymers obtained by ATRP for nucleic acid delivery Journal Article
In: International Journal of Pharmaceutics, vol. 466, no 1-2, pp. 246–257, 2014.
Abstract | Links | BibTeX | Tags: ATRP, DNA delivery, Polyaspartamide, SiRNA delivery
@article{Cavallaro2014b,
title = {Synthesis and characterization of polyaspartamide copolymers obtained by ATRP for nucleic acid delivery},
author = {Gennara Cavallaro and Mariano Licciardi and Giovanni Amato and Carla Sardo and Gaetano Giammona and Rossella Farra and Barbara Dapas and Mario Grassi and Gabriele Grassi},
url = {http://www.sciencedirect.com/science/article/pii/S0378517314001690},
doi = {10.1016/j.ijpharm.2014.03.026},
year = {2014},
date = {2014-05-15},
journal = {International Journal of Pharmaceutics},
volume = {466},
number = {1-2},
pages = {246\textendash257},
abstract = {Nucleic acid molecules such as small interfering RNAs (siRNAs) and plasmidic DNAs (pDNAs) have been shown to have the potential to be of therapeutic value in different human diseases. Their practical use is however compromised by the lack of appropriate release systems. Delivered as naked molecules, siRNAs/pDNAs are rapidly degraded by extracellular nucleases thus considerably reducing the amount of molecule which can reach the target cells. Additionally, the anionic charge of the phosphate groups present on the siRNAs/pDNAs backbone, disfavors the interaction with the negatively charged surface of the cell membrane.
In this paper we describe the generation of a novel polymer able to deliver both siRNAs and pDNAs. The combined release of these molecules is used in many different experimental settings such as the evaluation of the silencing efficiency of a given siRNA targeted against a given RNA, encoded by the pDNA. The possibility to use the same delivery system is very convenient from the technical point of view and it allows minimizing possible artifacts introduced by the use of different delivery agents for siRNAs and pDNA.
The copolymer described here is based on α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) bearing positively chargeable side oligochains, with diethylamino ethyl methacrylate (DEAEMA) as monomer. Monomer polymerization has been obtained by atom transfer radical polymerization (ATRP), a technique which allows the precise polymerization of the monomer. In addition to the chemical\textendashphysical characterization of the polymer, we provide evidences of the polymer ability to delivery both siRNAs and pDNA to cultured cells. Whereas additional investigations are necessary to study the delivery mechanisms of this polyplex, the polymer generated represents a novel and convenient device for the delivery of both siRNAs and pDNA.},
keywords = {ATRP, DNA delivery, Polyaspartamide, SiRNA delivery},
pubstate = {published},
tppubtype = {article}
}
In this paper we describe the generation of a novel polymer able to deliver both siRNAs and pDNAs. The combined release of these molecules is used in many different experimental settings such as the evaluation of the silencing efficiency of a given siRNA targeted against a given RNA, encoded by the pDNA. The possibility to use the same delivery system is very convenient from the technical point of view and it allows minimizing possible artifacts introduced by the use of different delivery agents for siRNAs and pDNA.
The copolymer described here is based on α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) bearing positively chargeable side oligochains, with diethylamino ethyl methacrylate (DEAEMA) as monomer. Monomer polymerization has been obtained by atom transfer radical polymerization (ATRP), a technique which allows the precise polymerization of the monomer. In addition to the chemical–physical characterization of the polymer, we provide evidences of the polymer ability to delivery both siRNAs and pDNA to cultured cells. Whereas additional investigations are necessary to study the delivery mechanisms of this polyplex, the polymer generated represents a novel and convenient device for the delivery of both siRNAs and pDNA.
Cascone, Sara; Lamberti, Gaetano; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela
Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis Journal Article
In: Carbohydrate Polymers, vol. 103, pp. 348–354, 2014, ISSN: 01448617.
Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogels, Texture analysis, Water content
@article{Cascone2014,
title = {Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis},
author = { Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba},
url = {http://www.sciencedirect.com/science/article/pii/S0144861713012757},
doi = {10.1016/j.carbpol.2013.12.060},
issn = {01448617},
year = {2014},
date = {2014-03-01},
journal = {Carbohydrate Polymers},
volume = {103},
pages = {348--354},
abstract = {The use of hydrogels in the preparation of controlled release pharmaceutical forms is extensively diffused. The main feature of these polymers is their ability to swell forming a gel layer when they enter in contact with fluids. Once the gel layer is formed, the drug contained in the matrix can easily diffuse ensuring a controlled release from the tablet. Measurement of water content within a hydrating matrix based on hydrogels is a key topic in the study of pharmaceutical solid dosage forms. The aim of this work is to evaluate the water content of swollen matrices composed by HPMC and theophylline both in axial and in radial direction, as a function of time, using a texture analysis. A relationship between water content and slope of the force\textendashpenetration curves has been obtained using a simplified system in which the water uptake is allowed only in radial direction, obtaining thus partially hydrated matrices with the water content varying only along the radial direction. Once the relationship has been validated, it has been applied in a more complex system in which the polymer swelling takes place in both axial and radial direction. Thus, using the texture analysis it has been possible to determine the water in each position within the hydrated matrices.},
keywords = {Hydrogel Characterization, Hydrogels, Texture analysis, Water content},
pubstate = {published},
tppubtype = {article}
}
Abrami, Michela; D'Agostino, Ilenia; Milcovich, Gesmi; Fiorentino, Simona; Farra, Rossella; Asaro, Fioretta; Lapasin, Romano; Grassi, Gabriele; Grassi, Mario
Physical characterization of alginate-Pluronic F127 gel for endoluminal NABDs delivery Journal Article
In: Soft Matter, vol. 10, pp. 729-737, 2014.
Abstract | Links | BibTeX | Tags:
@article{Abrami2014,
title = {Physical characterization of alginate-Pluronic F127 gel for endoluminal NABDs delivery},
author = {Michela Abrami and Ilenia D'Agostino and Gesmi Milcovich and Simona Fiorentino and Rossella Farra and Fioretta Asaro and Romano Lapasin and Gabriele Grassi and Mario Grassi},
url = {http://pubs.rsc.org/en/Content/ArticleLanding/2014/SM/C3SM51873F#!divAbstract},
doi = {10.1039/C3SM51873F },
year = {2014},
date = {2014-02-07},
journal = {Soft Matter},
volume = {10},
pages = {729-737},
abstract = {Here we focus the attention on the physical characteristics of a highly biocompatible hydrogel made up of crosslinked alginate and Pluronic F127 (PF127). This is a composite polymeric blend we propose for artery endoluminal delivery of an emerging class of molecules named nucleic acid based drugs (NABDs). The physical characterization of our composite gel, i.e. mesh size distribution and PF127-alginate mutual organization after crosslinking, can significantly determine the NABDs release kinetics. Thus, to explore these aspects, different technical approaches, i.e. rheology, low/high field NMR and TEM, were used. While rheology provided information at the macroscopic and nano-level, the other three approaches gave details at the nano-level. We observe that Pluronic micelles, organizing in cubic ordered domains, generate, upon alginate crosslinking, the formation of meshes (≈ 150 nm) larger than those occurring in a Pluronic-free alginate network (≈ 25 nm). Nevertheless, smaller alginate meshes are still on and can just host un-structured Pluronic micelles and water. Accordingly, the gel structure is quite inhomogeneous, where big meshes (filled by crystalline Pluronic) co-exist with smaller meshes (hosting water and un-structured PF127 micelles). While big meshes offer a considerable hindering action on a diffusing solute, smaller ones represent a sort of free space where solute diffusion is faster. The presence of big and small meshes indicates that drug release may follow a double kinetics characterized by a fast and slow release. Notably, this behavior is considered appropriate for endoluminal drug release to the arterial wall.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Dalmoro, Annalisa; Barba, Anna Angela; D'Amore, Matteo; Lamberti, Gaetano
Single-Pot Semicontinuous Bench Scale Apparatus To Produce Microparticles Journal Article
In: Industrial & Engineering Chemistry Research, vol. 53, no 7, pp. 2771–2780, 2014, ISSN: 0888-5885.
Abstract | Links | BibTeX | Tags: Micro and Nano Vectors
@article{Dalmoro2014,
title = {Single-Pot Semicontinuous Bench Scale Apparatus To Produce Microparticles},
author = { Annalisa Dalmoro and Anna Angela Barba and Matteo D'Amore and Gaetano Lamberti},
url = {http://pubs.acs.org/doi/abs/10.1021/ie403308q},
doi = {10.1021/ie403308q},
issn = {0888-5885},
year = {2014},
date = {2014-02-01},
journal = {Industrial \& Engineering Chemistry Research},
volume = {53},
number = {7},
pages = {2771--2780},
publisher = {ACS Publications},
abstract = {This work presents both the design of a novel process to produce microparticles with a shell−core structure and a bench scale apparatus purposely realized. The developed process was designed to respond to mandatory needs of process intensification. It involved the coupling of two emergent technologies: atomization assisted by ultrasonic energy and microwave heating. The former was used to atomize polymeric solutions; the latter was applied to stabilize the produced droplets by drying. Both operations were performed in the same vessel with the aim to have a single-pot process chamber and were carried out by a semicontinuous procedure. Basic design criteria and advantages of the ultrasonic−microwave coupled operations in the realized apparatus are presented and discussed. Results of testing and of operating runs to produce shell−core microparticles are also reported, emphasizing the main features of the produced particles.},
keywords = {Micro and Nano Vectors},
pubstate = {published},
tppubtype = {article}
}
Lanotte, Luca; Tomaiuolo, Giovanna; Misbah, Chaouqi; Bureau, Lionel; Guido, Stefano
Red blood cell dynamics in polymer brush-coated microcapillaries: A model of endothelial glycocalyx in vitro Journal Article
In: Biomicrofluidics, vol. 8, no 014104, 2014.
Abstract | Links | BibTeX | Tags:
@article{Lanotte2014,
title = {Red blood cell dynamics in polymer brush-coated microcapillaries: A model of endothelial glycocalyx in vitro},
author = {Luca Lanotte and Giovanna Tomaiuolo and Chaouqi Misbah and Lionel Bureau and Stefano Guido},
url = {http://scitation.aip.org/content/aip/journal/bmf/8/1/10.1063/1.4863723},
doi = {10.1063/1.4863723},
year = {2014},
date = {2014-01-29},
journal = {Biomicrofluidics},
volume = {8},
number = {014104},
abstract = {The confined flow of red blood cells (RBCs) in microvasculature is essential for oxygen delivery to body tissues and has been extensively investigated in the literature, both in vivo and in vitro. One of the main problems still open in microcirculation is that flow resistance in microcapillaries in vivo is higher than that in vitro. This discrepancy has been attributed to the glycocalyx, a macromolecular layer lining the inner walls of vessels in vivo, but no direct experimental evidence of this hypothesis has been provided so far. Here, we investigate the flow behavior of RBCs in glass microcapillaries coated with a polymer brush (referred to as “hairy” microcapillaries as opposed to “bare” ones with no coating), an experimental model system of the glycocalyx. By high-speed microscopy imaging and image analysis, a velocity reduction of RBCs flowing in hairy microcapillaries as compared to bare ones is indeed found at the same pressure drop. Interestingly, such slowing down is larger than expected from lumen reduction due to the polymer brush and displays an on-off trend with a threshold around 70 nm of polymer brush dry thickness. Above this threshold, the presence of the polymer brush is associated with an increased RBC deformation, and RBC velocity is independent on polymer brush thickness (at the same pressure drop). In conclusion, this work provides direct support to the hypothesis that the glycocalyx is the main factor responsible of the higher flow resistance found in microcapillaries in vivo.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Baiz, Daniele; Dapas, Barbara; Farra, Rossella; Scaggiante, Bruna; Pozzato, Gabriele; Zanconati, Fabrizio; Fiotti, Nicola; Consoloni, Lara; Chiaretti, Sara; Grassi, Gabriele
Bortezomib effect on E2F and cyclin family members in human hepatocellular carcinoma cell lines Journal Article
In: World Journal of Gastroenterology, vol. 20, no 3, pp. 795 – 803, 2014.
Abstract | Links | BibTeX | Tags:
@article{Baiz2014,
title = {Bortezomib effect on E2F and cyclin family members in human hepatocellular carcinoma cell lines},
author = {Daniele Baiz and Barbara Dapas and Rossella Farra and Bruna Scaggiante and Gabriele Pozzato and Fabrizio Zanconati and Nicola Fiotti and Lara Consoloni and Sara Chiaretti and Gabriele Grassi},
url = {http://www.wjgnet.com/1007-9327/full/v20/i3/795.htm},
doi = {10.3748/wjg.v20.i3.795},
year = {2014},
date = {2014-01-21},
journal = {World Journal of Gastroenterology},
volume = {20},
number = {3},
pages = {795 \textendash 803},
abstract = {AIM
To evaluate the effects of the proteasome inhibitor Bortezomib (BZB) on E2Fs and related genes in Hepatocellular carcinoma (HCC) cells.
METHODS
The mRNA levels of the E2F family members (pro-proliferative: E2F1-3 and anti-proliferative: E2F4-8) and of their related genes cyclins and cyclin-dependent kinases (cdks) were evaluated in two HCC cell lines following a single BZB administration. mRNA levels of the epithelial-mesenchymal transition (EMT) genes were also measured in both cell lines after BZB treatment. The BZB concentration (40 nM) used was chosen to stay well below the maximal amount/cm2 recommended for in vivo application, and two days incubation was chosen as this time point has been found optimal to detect BZB effects in our previous studies. The HCC cell lines, HepG2 and JHH6, were chosen as they display different phenotypes, hepatocyte-like for HepG2 and undifferentiated for JHH6, thus representing an in vitro model of low and high aggressive forms of HCC, respectively. The mRNA levels of the target genes were measured by two-color microarray-based gene expression analysis, performed according to Agilent Technologies protocol and using an Agilent Scan B. For the E2F family members, mRNA levels were quantified by RT-PCR. Using small interfering RNA’s, the effects of E2F8 depletion on cell number was also evaluated.
RESULTS
After BZB treatment, microarray analysis of the undifferentiated JHH6 revealed a significant decrease in the expression of the pro-proliferative E2F member E2F2. Quantitative RT-PCR data were in keeping with the microarray analysis, and showed a significant increase and decrease in E2F8 and E2F2 mRNA levels, respectively. In contrast, BZB treatment of the hepatocyte-like HCC cell line HepG2 had a significant impact on mRNA levels of 5 of the 8 E2F members. In particular, mRNA levels of the pro-proliferative E2F members E2F1, E2F2, and of the anti-proliferative member E2F8, decreased over 80%. Notably, a reduction in E2F8 expression in HepG2 and JHH6 cells following siRNA treatment had no impact on cell proliferation. As observed with JHH6, BZB treatment of HepG2 cells induced a significant increase in mRNA levels of an anti-proliferative E2F member, E2F6 in this case.
As was observed with E2F’s, more dramatic changes in mRNA levels of the E2F related genes cyclins and Cdks and the epithelial-mesenchymal transition (EMT) genes were observed after BTZ treatment of HepG2 compared to JHH6 .
CONCLUSION
The differential expression of E2Fs and related genes induced by BZB in diverse HCC cell phenotypes contribute to bortezomib’s mechanism of action in hepatocellular carcinoma.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
To evaluate the effects of the proteasome inhibitor Bortezomib (BZB) on E2Fs and related genes in Hepatocellular carcinoma (HCC) cells.
METHODS
The mRNA levels of the E2F family members (pro-proliferative: E2F1-3 and anti-proliferative: E2F4-8) and of their related genes cyclins and cyclin-dependent kinases (cdks) were evaluated in two HCC cell lines following a single BZB administration. mRNA levels of the epithelial-mesenchymal transition (EMT) genes were also measured in both cell lines after BZB treatment. The BZB concentration (40 nM) used was chosen to stay well below the maximal amount/cm2 recommended for in vivo application, and two days incubation was chosen as this time point has been found optimal to detect BZB effects in our previous studies. The HCC cell lines, HepG2 and JHH6, were chosen as they display different phenotypes, hepatocyte-like for HepG2 and undifferentiated for JHH6, thus representing an in vitro model of low and high aggressive forms of HCC, respectively. The mRNA levels of the target genes were measured by two-color microarray-based gene expression analysis, performed according to Agilent Technologies protocol and using an Agilent Scan B. For the E2F family members, mRNA levels were quantified by RT-PCR. Using small interfering RNA’s, the effects of E2F8 depletion on cell number was also evaluated.
RESULTS
After BZB treatment, microarray analysis of the undifferentiated JHH6 revealed a significant decrease in the expression of the pro-proliferative E2F member E2F2. Quantitative RT-PCR data were in keeping with the microarray analysis, and showed a significant increase and decrease in E2F8 and E2F2 mRNA levels, respectively. In contrast, BZB treatment of the hepatocyte-like HCC cell line HepG2 had a significant impact on mRNA levels of 5 of the 8 E2F members. In particular, mRNA levels of the pro-proliferative E2F members E2F1, E2F2, and of the anti-proliferative member E2F8, decreased over 80%. Notably, a reduction in E2F8 expression in HepG2 and JHH6 cells following siRNA treatment had no impact on cell proliferation. As observed with JHH6, BZB treatment of HepG2 cells induced a significant increase in mRNA levels of an anti-proliferative E2F member, E2F6 in this case.
As was observed with E2F’s, more dramatic changes in mRNA levels of the E2F related genes cyclins and Cdks and the epithelial-mesenchymal transition (EMT) genes were observed after BTZ treatment of HepG2 compared to JHH6 .
CONCLUSION
The differential expression of E2Fs and related genes induced by BZB in diverse HCC cell phenotypes contribute to bortezomib’s mechanism of action in hepatocellular carcinoma.
Scaggiante, Bruna; Kazemi, Maryam; Pozzato, Gabriele; Dapas, Barbara; Farra, Rosella; Grassi, Mario; Zanconati, Fabrizio; Grassi, Gabriele
Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials Journal Article
In: World Journal of Gastroenterology, vol. 20, no 5, pp. 1268-1288, 2014.
Abstract | Links | BibTeX | Tags:
@article{Scaggiante2014,
title = {Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials},
author = {Bruna Scaggiante and Maryam Kazemi and Gabriele Pozzato and Barbara Dapas and Rosella Farra and Mario Grassi and Fabrizio Zanconati and Gabriele Grassi},
url = {http://www.wjgnet.com/1007-9327/full/v20/i5/1268.htm},
doi = {10.3748/wjg.v20.i5.1268},
year = {2014},
date = {2014-01-21},
journal = {World Journal of Gastroenterology},
volume = {20},
number = {5},
pages = {1268-1288},
abstract = {Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the sixth most common cancer worldwide and the third leading cause of cancer-related death. The difficulty to diagnose early cancer stages, the aggressive behaviors of HCC, and the poor effectiveness of therapeutic treatments, represent the reasons for the quite similar deaths per year and incidence number.
Considering the fact that the diagnosis of HCC typically occurs in the advanced stages of the disease when the therapeutic options have only modest efficacy, the possibility to identify early diagnostic markers could be of significant benefit. So far, a large number of biomarkers have been associated to HCC progression and aggressiveness, but many of them turned out not to be of practical utility. This is the reason why active investigations are ongoing in this field.
Given the huge amount of published works aimed at the identification of HCC biomarkers, in this review we mainly focused on the data published in the last year, with particular attention to the role of 1) molecular and biochemical cellular markers, 2) micro-interfering RNAs (miRNAs), 3) epigenetic variations, and 4) tumor stroma. It is worth mentioning that a significant number of the HCC markers described in the present review may be utilized also as targets for novel therapeutic approaches, indicating the tight relation between diagnosis and therapy.
In conclusion, we believe that integrated researches among the different lines of investigation indicated above, should represent the winning strategies to identify effective HCC markers and therapeutic targets.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Considering the fact that the diagnosis of HCC typically occurs in the advanced stages of the disease when the therapeutic options have only modest efficacy, the possibility to identify early diagnostic markers could be of significant benefit. So far, a large number of biomarkers have been associated to HCC progression and aggressiveness, but many of them turned out not to be of practical utility. This is the reason why active investigations are ongoing in this field.
Given the huge amount of published works aimed at the identification of HCC biomarkers, in this review we mainly focused on the data published in the last year, with particular attention to the role of 1) molecular and biochemical cellular markers, 2) micro-interfering RNAs (miRNAs), 3) epigenetic variations, and 4) tumor stroma. It is worth mentioning that a significant number of the HCC markers described in the present review may be utilized also as targets for novel therapeutic approaches, indicating the tight relation between diagnosis and therapy.
In conclusion, we believe that integrated researches among the different lines of investigation indicated above, should represent the winning strategies to identify effective HCC markers and therapeutic targets.
Barba, Anna Angela; Dalmoro, Annalisa; D'Amore, Matteo; Vascello, Clara; Lamberti, Gaetano
Biocompatible nano-micro-particles by solvent evaporation from multiple emulsions technique Journal Article
In: Journal of Materials Science, vol. 49, no 14, pp. 5160–5170, 2014, ISSN: 0022-2461.
Abstract | Links | BibTeX | Tags: Micro and Nano Vectors
@article{Barba2014c,
title = {Biocompatible nano-micro-particles by solvent evaporation from multiple emulsions technique},
author = { Anna Angela Barba and Annalisa Dalmoro and Matteo D'Amore and Clara Vascello and Gaetano Lamberti},
url = {http://link.springer.com/10.1007/s10853-014-8224-1},
doi = {10.1007/s10853-014-8224-1},
issn = {0022-2461},
year = {2014},
date = {2014-01-01},
journal = {Journal of Materials Science},
volume = {49},
number = {14},
pages = {5160--5170},
publisher = {Springer US},
abstract = {In this study, a method based on a multiple emulsions system was developed for the production of polymeric nano and micro-vectors. The possibility to apply an unified preparation technique to different polymers, such as polyesters [polycaprolactone, poly-dl-lactide, poly(dl-lactide-co-caprolactone) = 70/30] and polyacrylates [poly(methylmethacrylate\textendashacrylic acid) = 73/27], loaded with different model molecules (budesonide, tamoxifen, and $alpha$-tocopherol) was explored. After selecting the best operating conditions, especially for emulsification and separation, the technique proved to be readily adaptable for production of both nano and micro-particles with different morphologies, depending on type of polymer, and consequently on solvent used for solubilization: nano-particles, with a round shape and a smooth surface, for polyesters, otherwise micro-particles for the polyacrylate polymer, owing to the presence of hydrophilic co-solvents, that caused both an easy coalescence between the oil and water phases, thus enlarged particles size, and a high porosity. Even the yield of encapsulation was influenced by the presence of hydrophilic co-solvents, causing a higher yield for nano-vectors. Polyesters-based nano-vectors showed release times of molecules, linked to their degradation time, higher than 8 months that make them useful to formulate injectable or implantable drug delivery systems. Polyacrylate-based micro-vectors showed an enteric behavior, interesting for designing solid pharmaceutical formulations for oral delivery. Therefore, the technique demonstrated to assure a broad application in drug delivery research.},
keywords = {Micro and Nano Vectors},
pubstate = {published},
tppubtype = {article}
}
Bochicchio, Sabrina; Dalmoro, Annalisa; Barba, Anna Angela; Grassi, Gabriele; Lamberti, Gaetano
Liposomes as siRNA Delivery Vectors Journal Article
In: Current drug metabolism, vol. 15, no 9, pp. 882–892, 2014, ISSN: 1389-2002.
Abstract | Links | BibTeX | Tags: Drug Delivery Systems, liposome, Micro and Nano Vectors, siRNA
@article{Bochicchio2014,
title = {Liposomes as siRNA Delivery Vectors},
author = {Sabrina Bochicchio and Annalisa Dalmoro and Anna Angela Barba and Gabriele Grassi and Gaetano Lamberti},
url = {http://www.eurekaselect.com/128256/article},
doi = {10.2174/1389200216666150206124913},
issn = {1389-2002},
year = {2014},
date = {2014-01-01},
journal = {Current drug metabolism},
volume = {15},
number = {9},
pages = {882--892},
publisher = {Bentham Science Publishers},
abstract = {Nucleic Acid Based Drugs (NABDs) constitute a class of promising and powerful therapeutic new agents with limited side effects, potentially useable against a wide range of diseases, including cancer. Among them, the short interfering RNAs (siRNAs), represent very effective molecules. Despite their in vitro efficacy, the major drawback that limits siRNAs usage consists in a difficult delivery due to their very low stability in physiological fluids, and to their limited membrane-permeability through physiological barriers. On the other hand, the liposomes (lipid bilayers closed in vesicles of various sizes) represent interesting drug delivery systems (DDSs) which can be tailored in order to get the best performance in terms of load, vesicle size and transfection yield. In this work, the current state of study in these two fields, and the connections between them, are briefly summarized.},
keywords = {Drug Delivery Systems, liposome, Micro and Nano Vectors, siRNA},
pubstate = {published},
tppubtype = {article}
}
Barba, Anna Angela; Lamberti, Gaetano; Rabbia, Luca; Grassi, Mario; Larobina, Domenico; Grassi, Gabriele
Modeling of the reticulation kinetics of alginate/pluronic blends for biomedical applications Journal Article
In: Materials Science and Engineering: C, vol. 37, pp. 327–331, 2014, ISSN: 09284931.
Abstract | Links | BibTeX | Tags: Alginate, Hydrogel Modeling, Modeling, Pluronic, Reticulation
@article{Barba2014b,
title = {Modeling of the reticulation kinetics of alginate/pluronic blends for biomedical applications},
author = { Anna Angela Barba and Gaetano Lamberti and Luca Rabbia and Mario Grassi and Domenico Larobina and Gabriele Grassi},
url = {http://www.sciencedirect.com/science/article/pii/S0928493114000423},
doi = {10.1016/j.msec.2014.01.034},
issn = {09284931},
year = {2014},
date = {2014-01-01},
journal = {Materials Science and Engineering: C},
volume = {37},
pages = {327--331},
abstract = {In this work, blends of alginate/pluronic (F127) for biomedical applications were investigated. In particular, the kinetics of alginate chain reticulation by bivalent cations was studied by experimental and modeling approaches. Two kinds of sodium alginate were tested to obtain hard gel films. The thicknesses of the reticulated alginate films were measured as function of the exposure time and of the reticulating copper (Cu2+) solution concentration. The kinetics was described by a proper model able to reproduce the experimental data. The model parameters, evaluated based on the measurements of thicknesses as function of Cu2+ concentration and exposure time, were further validated by comparing the prediction of the model with another set of independent measurement; here, the depletion of Cu2+ ions in the conditioning solution above the reacting gel is measured as function of time. The tuned model could be used in the description of the future applications of the blends.},
keywords = {Alginate, Hydrogel Modeling, Modeling, Pluronic, Reticulation},
pubstate = {published},
tppubtype = {article}
}
Barba, Anna Angela; Bochicchio, Sabrina; Lamberti, Gaetano; Dalmoro, Annalisa
Ultrasonic energy in liposome production: process modelling and size calculation Journal Article
In: Soft Matter, vol. 10, no 15, pp. 2574, 2014, ISSN: 1744-683X.
Abstract | Links | BibTeX | Tags: Micro and Nano Vectors
@article{Barba2014a,
title = {Ultrasonic energy in liposome production: process modelling and size calculation},
author = { Anna Angela Barba and Sabrina Bochicchio and Gaetano Lamberti and Annalisa Dalmoro},
url = {http://xlink.rsc.org/?DOI=c3sm52879k},
doi = {10.1039/c3sm52879k},
issn = {1744-683X},
year = {2014},
date = {2014-01-01},
journal = {Soft Matter},
volume = {10},
number = {15},
pages = {2574},
publisher = {The Royal Society of Chemistry},
abstract = {The use of liposomes in several fields of biotechnology, as well as in pharmaceutical and food sciences is continuously increasing. Liposomes can be used as carriers for drugs and other active molecules. Among other characteristics, one of the main features relevant to their target applications is the liposome size. The size of liposomes, which is determined during the production process, decreases due to the addition of energy. The energy is used to break the lipid bilayer into smaller pieces, then these pieces close themselves in spherical structures. In this work, the mechanisms of rupture of the lipid bilayer and the formation of spheres were modelled, accounting for how the energy, supplied by ultrasonic radiation, is stored within the layers, as the elastic energy due to the curvature and as the tension energy due to the edge, and to account for the kinetics of the bending phenomenon. An algorithm to solve the model equations was designed and the relative calculation code was written. A dedicated preparation protocol, which involves active periods during which the energy is supplied and passive periods during which the energy supply is set to zero, was defined and applied. The model predictions compare well with the experimental results, by using the energy supply rate and the time constant as fitting parameters. Working with liposomes of different sizes as the starting point of the experiments, the key parameter is the ratio between the energy supply rate and the initial surface area.},
keywords = {Micro and Nano Vectors},
pubstate = {published},
tppubtype = {article}
}
Cavallaro, Gennara; Triolo, Daniela; Licciardi, Mariano; Giammona, Gaetano; Chirico, Giuseppe; Sironi, Laura; Dacarro, Giacomo; Donà, Alice; Milanese, Chiara; Pallavicini, Piersandro
Amphiphilic Copolymers Based on Poly[(hydroxyethyl)-d,l-aspartamide]: A Suitable Functional Coating for Biocompatible Gold Nanostars Journal Article
In: Biomacromolecules, vol. 14, no 12, pp. 4260–4270, 2014.
Abstract | Links | BibTeX | Tags:
@article{Cavallaro2014,
title = {Amphiphilic Copolymers Based on Poly[(hydroxyethyl)-d,l-aspartamide]: A Suitable Functional Coating for Biocompatible Gold Nanostars},
author = {Gennara Cavallaro and Daniela Triolo and Mariano Licciardi and Gaetano Giammona and Giuseppe Chirico and Laura Sironi and Giacomo Dacarro and Alice Don\`{a} and Chiara Milanese and Piersandro Pallavicini},
url = {http://pubs.acs.org/doi/abs/10.1021/bm401130z},
doi = {10.1021/bm401130z},
year = {2014},
date = {2014-01-01},
journal = {Biomacromolecules},
volume = {14},
number = {12},
pages = {4260\textendash4270},
abstract = {Novel amphiphilic copolymers have been synthesized based on a biocompatible poly(hydroxyethylaspartamide) (PHEA) backbone, bearing both anchoring groups for gold nanoparticles, such as thiols and disulfide, and conjugable moieties, such as amino groups, the latter as points suitable for appending further functional agents. The strategy was to functionalize α,β-poly[(N-2-hydroxyethyl)-D,L-aspartamide] (PHEA) with PEG2000-NH2 and with ethylenediamine (EDA) obtaining a partially pegylated copolymer with a large number of pendant primary amino groups. A fraction of the latter was conjugated with molecules bearing terminal thiol moieties such as 12-mercaptododecanoic acid (MDA) and disulfide groups such as lipoic acid (LA), obtaining the two amphiphilic derivatives PHEA-PEG2000-EDA-MDA (PPE-MDA) and PHEA-PEG2000-EDA-LA (PPE-LA), which also proved intrinsically able to self-assemble in polymeric micelles. The two copolymers efficiently coated gold nanostars (GNSs, size ≈ 40 nm), wrapping around the surface increasing only slightly the hydrodynamic diameter (reaching ≈ 45 nm), imparting them stability and a pH-switchable surface charge, due to the unreacted amino groups. Remarkably, the poor solvation and the huge steric hindrance experienced by the amino groups lowers the observed logarithmic protonation constants to 5.6-5.7. In vitro experiments demonstrated that PPE-MDA and PPE-LA copolymers have an intrinsic excellent biocompatibility in both the human brain neuroblastoma (SH-SY5Y) and human bronchial epithelial (16-HBE) cell lines. Interaction of the same cell lines with "nude" GNS and GNS coated with PPE-LA was also studied, disclosing a completely satisfactory biocompatibility of the latter.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Trapani, Adriana; Gioia, Sante Di; Castellani, Stefano; Carbone, Annalucia; Cavallaro, Gennara; Trapani, Giuseppe; Conese, Massimo
Nanocarriers for respiratory diseases treatment: recent advances and current challenges Journal Article
In: Current Topics in Medicinal Chemistry, vol. 14, no 9, pp. 1133 - 1147, 2014.
Abstract | Links | BibTeX | Tags: Defense mechanisms, inhalation of polymeric- and lipid-based nanocarriers, lung targeting, mucus penetration, pulmonary delivery, respiratory diseases
@article{Trapani2014,
title = {Nanocarriers for respiratory diseases treatment: recent advances and current challenges},
author = {Adriana Trapani and Sante {Di Gioia} and Stefano Castellani and Annalucia Carbone and Gennara Cavallaro and Giuseppe Trapani and Massimo Conese},
url = {http://www.eurekaselect.com/121255/article},
doi = {10.2174/1568026614666140329225817},
year = {2014},
date = {2014-01-01},
journal = {Current Topics in Medicinal Chemistry},
volume = {14},
number = {9},
pages = {1133 - 1147},
abstract = {Pulmonary delivery of locally-acting drugs encapsulated in nanocarriers provides several advantages for the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis, tuberculosis and lung cancer. These advantages include, among others, sustained drug delivery to the lungs, reduced therapeutic dose and improved patient compliance. The aim of this review is to give an updated overview on recent advances recorded in the last few years in this field as well as on the major challenges still existing and that remain to be overcome before any clinical application. After an outline on the cellular and extracellular barriers affecting drug delivery to the airways both in physiological and pathological conditions, the significant developments recorded using inhaled polymeric- and lipid-based nanocarriers for drug and gene delivery to the lung are presented. In this discussion, the major challenges existing in the field are evidenced including the understanding of the factors governing the mucus penetration capability of these nanocarriers and the identification of new technologies for delivering drugs to specific regions or cell types of the lungs. In this regard, the recognition of receptor expressed only at lung level may facilitate drug targeting to this organ and it should improve the therapeutic efficacy of nanocarrier-based treatments for respiratory diseases. },
keywords = {Defense mechanisms, inhalation of polymeric- and lipid-based nanocarriers, lung targeting, mucus penetration, pulmonary delivery, respiratory diseases},
pubstate = {published},
tppubtype = {article}
}
2013
Hasa, Dritan; Voinovich, Dario; Perissutti, Beatrice; Grassi, Gabriele; Fiorentino, Simona; Farra, Rossella; Abrami, Michela; Colombo, Italo; Grassi, Mario
Reduction of melting temperature and enthalpy of drug crystals: Theoretical aspects Journal Article
In: European Journal of Pharmaceutical Sciences, vol. 50, no 1, pp. 17–28, 2013.
Abstract | Links | BibTeX | Tags:
@article{Hasa2013,
title = {Reduction of melting temperature and enthalpy of drug crystals: Theoretical aspects},
author = {Dritan Hasa and Dario Voinovich and Beatrice Perissutti and Gabriele Grassi and Simona Fiorentino and Rossella Farra and Michela Abrami and Italo Colombo and Mario Grassi },
url = {http://www.sciencedirect.com/science/article/pii/S0928098713001267},
doi = {10.1016/j.ejps.2013.03.018},
year = {2013},
date = {2013-09-27},
journal = {European Journal of Pharmaceutical Sciences},
volume = {50},
number = {1},
pages = {17\textendash28},
abstract = {This review deals with the mathematical models describing the reduction of melting temperature and enthalpy of solids in the nano-size range. In particular, the attention focuses on the thermodynamic based models that are theoretically solid and can be suitably used in the case of organic drugs. Indeed, while much effort has been put in the past to study the melting of metal nano-crystals, little work has been done for organic drug nano-crystals. However, due to the high potential of drug nano-crystals (their solubility increases with size reduction), this theme has become more and more important in the pharmaceutical field. Accordingly, this review, after illustrating the physical frame of drug melting, focuses on the thermodynamic aspects required to describe the melting of spherical and not spherical nano-crystals. Finally, the reliability of some models is tested against the results coming from X-rays analysis in the case of two organic drugs (griseofulvin and nifedipine). This test proved models strength.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cascone, Sara; Lamberti, Gaetano; Titomanlio, Giuseppe; Piazza, Ornella
Pharmacokinetics of Remifentanil: a three-compartmental modeling approach Journal Article
In: Translational Medicine @ UniSa, vol. 7, pp. 18–22, 2013, ISSN: 2239-9747.
Abstract | Links | BibTeX | Tags: In silico, Pharmacokinetics
@article{Cascone2013,
title = {Pharmacokinetics of Remifentanil: a three-compartmental modeling approach},
author = { Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio and Ornella Piazza},
url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829787/},
issn = {2239-9747},
year = {2013},
date = {2013-09-01},
journal = {Translational Medicine @ UniSa},
volume = {7},
pages = {18--22},
publisher = {Universit},
abstract = {Remifentanil is a new opioid derivative drug characterized by a fast onset and by a short time of action, since it is rapidly degraded by esterases in blood and other tissues. Its pharmacokinetic and pharmacodynamics properties make remifentanil a very interesting molecule in the field of 0anesthesia. However a complete and versatile pharmacokinetic description of remifentanil still lacks. In this work a three-compartmental model has been developed to describe the pharmacokinetics of remifentanil both in the case in which it is administered by intravenous constant-rate infusion and by bolus injection. The model curves have been compared with experimental data published in scientific papers and the model parameters have been optimized to describe both ways of administration. The ad hoc model is adaptable and potentially useful for predictive purposes.},
keywords = {In silico, Pharmacokinetics},
pubstate = {published},
tppubtype = {article}
}
Craparo, Emanuela Fabiola; Teresi, Girolamo; Licciardi, Mariano; Bondì, Maria Luisa; Cavallaro, Gennara
Novel composed galactosylated nanodevices containing a ribavirin prodrug as hepatic cell-targeted carriers for HCV treatment. Journal Article
In: Journal of Biomedical Nanotechnology, vol. 9, pp. 1107-1122, 2013.
Abstract | Links | BibTeX | Tags:
@article{Craparo2013b,
title = {Novel composed galactosylated nanodevices containing a ribavirin prodrug as hepatic cell-targeted carriers for HCV treatment.},
author = {Emanuela Fabiola Craparo and Girolamo Teresi and Mariano Licciardi and Maria Luisa Bond\`{i} and Gennara Cavallaro},
url = {http://www.ingentaconnect.com/content/asp/jbn/2013/00000009/00000006/art00021?token=00511c23136123167419437a63736a6f5e47415d7d6646447b23796f644a467b4d616d3f4e4b347f2},
doi = {10.1166/jbn.2013.1608},
year = {2013},
date = {2013-06-06},
journal = {Journal of Biomedical Nanotechnology},
volume = {9},
pages = {1107-1122},
abstract = {In this paper, we describe the preparation of liver-targeted nanoparticles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors in the liver (i.e., ASGPR in hepatocytes). These particles were obtained starting from a galactosylated phospholipid-polyaminoacid conjugate. This latter was obtained by chemical reaction of poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide (PHEA-EDA) with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) sodium salt (DPPE), and subsequent reaction with lactose, obtaining PHEA-EDA-DPPE-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, i.e., RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. RBV tripalmitate-loaded nanoparticles were obtained starting from PHEA-EDADPPE-GAL copolymer by using the dialysis method. These particles showed spherical shape and nanometric size. By in vitro experiments the absence of haemolytic activity of RBV tripalmitate-loaded PHEA-EDA-DPPE-GAL nanoparticles and their specificity toward HepG2 were demonstrated by using a competitive inhibition assay in the presence of free GAL and assessing nanoparticle uptake in the presence of free GAL and/or non-galactosylated nanoparticles. This finding raises hope in terms of future nanoparticle-based liver-targeted drug delivery strategy for the hepatitis C treatment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Craparo, Emanuela Fabiola; Triolo, Daniela; Pitarresi, Giovanna; Giammona, Gaetano; Cavallaro, Gennara
Galactosylated Micelles for a Ribavirin Prodrug Targeting to Hepatocytes Journal Article
In: Biomacromolecules, vol. 14, no 6, pp. 1838-1849, 2013.
Abstract | Links | BibTeX | Tags:
@article{Craparo2013,
title = {Galactosylated Micelles for a Ribavirin Prodrug Targeting to Hepatocytes},
author = {Emanuela Fabiola Craparo and Daniela Triolo and Giovanna Pitarresi and Gaetano Giammona and Gennara Cavallaro},
url = {http://pubs.acs.org/doi/abs/10.1021/bm4002409},
doi = {10.1021/bm4002409},
year = {2013},
date = {2013-04-01},
journal = {Biomacromolecules},
volume = {14},
number = {6},
pages = {1838-1849},
abstract = {Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLAGAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver-targeted RBV tripalmitate-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size. By in vitro experiments, the specificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitive inhibition assay in the presence of free GAL. This finding raises hope in terms of future micelles-based liver-targeted drug delivery strategy for the hepatitis C treatment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Dalmoro, Annalisa; Barba, Anna Angela; D'Amore, Matteo
Analysis of Size Correlations for Microdroplets Produced by Ultrasonic Atomization Journal Article
In: The Scientific World Journal, vol. 2013, pp. 1–7, 2013, ISSN: 1537-744X.
Abstract | Links | BibTeX | Tags: Micro and Nano Vectors
@article{author,
title = {Analysis of Size Correlations for Microdroplets Produced by Ultrasonic Atomization},
author = { Annalisa Dalmoro and Anna Angela Barba and Matteo D'Amore},
url = {http://www.hindawi.com/journals/tswj/2013/482910/},
doi = {10.1155/2013/482910},
issn = {1537-744X},
year = {2013},
date = {2013-01-01},
journal = {The Scientific World Journal},
volume = {2013},
pages = {1--7},
abstract = {Microencapsulation techniques are widely applied in the field of pharmaceutical production to control drugs release in time and in physiological environments. Ultrasonic-assisted atomization is a new technique to produce microencapsulated systems by a mechanical approach. Interest in this technique is due to the advantages evidenceable (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) when comparing it to more conventional techniques. In this paper, the groundwork of atomization is introduced, the role of relevant parameters in ultrasonic atomization mechanism is discussed, and correlations to predict droplets size starting from process parameters and material properties are presented and tested.},
keywords = {Micro and Nano Vectors},
pubstate = {published},
tppubtype = {article}
}
Dalmoro, Annalisa; D'Amore, Matteo; Barba, Anna Angela
Droplet size prediction in the production of drug delivery microsystems by ultrasonic atomization. Journal Article
In: Translational medicine @ UniSa, vol. 7, no 2, pp. 6–11, 2013, ISSN: 2239-9747.
Abstract | Links | BibTeX | Tags: dimensionless, Micro and Nano Vectors, microparticles size prediction, numbers in atomization, ultrasonic atomization
@article{Dalmoro2013,
title = {Droplet size prediction in the production of drug delivery microsystems by ultrasonic atomization.},
author = { Annalisa Dalmoro and Matteo D'Amore and Anna Angela Barba},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3829785\&tool=pmcentrez\&rendertype=abstract},
issn = {2239-9747},
year = {2013},
date = {2013-01-01},
journal = {Translational medicine @ UniSa},
volume = {7},
number = {2},
pages = {6--11},
publisher = {Universit},
abstract = {Microencapsulation processes of drugs or other functional molecules are of great interest in pharmaceutical production fields. Ultrasonic assisted atomization is a new technique to produce microencapsulated systems by mechanical approach. It seems to offer several advantages (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) with respect to more conventional techniques. In this paper the groundwork of atomization is briefly introduced and correlations to predict droplet size starting from process parameters and material properties are presented.},
keywords = {dimensionless, Micro and Nano Vectors, microparticles size prediction, numbers in atomization, ultrasonic atomization},
pubstate = {published},
tppubtype = {article}
}
Lamberti, Gaetano; Cascone, Sara; Cafaro, Maria Margherita; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela
Measurements of water content in hydroxypropyl-methyl-cellulose based hydrogels via texture analysis. Journal Article
In: Carbohydrate polymers, vol. 92, no 1, pp. 765–8, 2013, ISSN: 1879-1344.
Abstract | Links | BibTeX | Tags: HPMC, Hydrogel Characterization, Texture analysis, Water content
@article{Lamberti2013a,
title = {Measurements of water content in hydroxypropyl-methyl-cellulose based hydrogels via texture analysis.},
author = { Gaetano Lamberti and Sara Cascone and Maria Margherita Cafaro and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba},
url = {http://www.sciencedirect.com/science/article/pii/S0144861712010193},
doi = {10.1016/j.carbpol.2012.10.003},
issn = {1879-1344},
year = {2013},
date = {2013-01-01},
journal = {Carbohydrate polymers},
volume = {92},
number = {1},
pages = {765--8},
abstract = {In this work, a fast and accurate method to evaluate the water content in a cellulose derivative-based matrix subjected to controlled hydration was proposed and tuned. The method is based on the evaluation of the work of penetration required in the needle compression test. The work of penetration was successfully related to the hydrogel water content, assayed by a gravimetric technique. Moreover, a fitting model was proposed to correlate the two variables (the water content and the work of penetration). The availability of a reliable tool is useful both in the quantification of the water uptake phenomena, both in the management of the testing processes of novel pharmaceutical solid dosage forms.},
keywords = {HPMC, Hydrogel Characterization, Texture analysis, Water content},
pubstate = {published},
tppubtype = {article}
}
Grassi, Gabriele; Scaggiante, Bruna; Dapas, Barbara; Farra, Rossella; Tonon, Federica; Lamberti, Gaetano; Barba, Anna Angela; Fiorentino, Simona; Fiotti, Nicola; Zanconati, Fabrizio; Abrami, Michela; Grassi, Mario
Therapeutic Potential of Nucleic Acid-Based Drugs in Coronary Hyper- Proliferative Vascular Diseases Journal Article
In: Current Medicinal Chemistry, vol. 20, no 18, pp. 3515 - 3538, 2013.
Abstract | Links | BibTeX | Tags:
@article{Grassi2013b,
title = {Therapeutic Potential of Nucleic Acid-Based Drugs in Coronary Hyper- Proliferative Vascular Diseases},
author = {Gabriele Grassi and Bruna Scaggiante and Barbara Dapas and Rossella Farra and Federica Tonon and Gaetano Lamberti and Anna Angela Barba and Simona Fiorentino and Nicola Fiotti and Fabrizio Zanconati and Michela Abrami and Mario Grassi },
url = {http://www.eurekaselect.com/113843/article},
doi = {10.2174/09298673113209990031},
year = {2013},
date = {2013-01-01},
journal = {Current Medicinal Chemistry},
volume = {20},
number = {18},
pages = {3515 - 3538},
abstract = {The thickening of the vessel wall (intimal hyperplasia) is a pathological process which often follows re-vascularization approaches such as transluminal angioplasty and artery bypass graft, procedures used to re-vascularize stenotic artery. Despite the significant improvements in the treatment of intimal hyperplasia obtained in the last years, the problem has not completely solved. Nucleic acid based-drugs (NABDs) represent an emergent class of molecules with potential therapeutic value for the treatment of intimal hyperplasia.
NABDs of interest in the field of intimal hyperplasia are: ribozymes, DNAzymes, antisense oligonucleotides, decoy oligonucleotides, small interfering RNAs and micro interfering RNAs. These molecules can recognize, in a sequence-specific fashion, a target which, depending on the different NABDs, can be represented by a nucleic acid or a protein. Upon binding, NABDs can down-modulate the functions of the target (mRNA/proteins) and thus they are used to impair the functions of disease-causing biological molecules. In spite of the great therapeutic potential demonstrated by NABDs in many experimental model of intima hyperplasia, their practical use is hindered by the necessity to identify optimal delivery systems to the vasculature.
In the first part of this review a brief description of the clinical problem related to intima hyperplasia formation after revascularization procedures is reported. In the second part, the attention is focused on the experimental evidences of NABD therapeutic potential in the prevention of intimal hyperplasia. Finally, in the third part, we will describe the strategies developed to optimize NABD delivery to the diseased vessel.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
NABDs of interest in the field of intimal hyperplasia are: ribozymes, DNAzymes, antisense oligonucleotides, decoy oligonucleotides, small interfering RNAs and micro interfering RNAs. These molecules can recognize, in a sequence-specific fashion, a target which, depending on the different NABDs, can be represented by a nucleic acid or a protein. Upon binding, NABDs can down-modulate the functions of the target (mRNA/proteins) and thus they are used to impair the functions of disease-causing biological molecules. In spite of the great therapeutic potential demonstrated by NABDs in many experimental model of intima hyperplasia, their practical use is hindered by the necessity to identify optimal delivery systems to the vasculature.
In the first part of this review a brief description of the clinical problem related to intima hyperplasia formation after revascularization procedures is reported. In the second part, the attention is focused on the experimental evidences of NABD therapeutic potential in the prevention of intimal hyperplasia. Finally, in the third part, we will describe the strategies developed to optimize NABD delivery to the diseased vessel.
Scaggiante, Bruna; Dapas, Barbara; Farra, Rossella; Grassi, Mario; Pozzato, Gabriele; Giansante, Carlo; Fiotti, Nicola; Tamai, Elisa; Tonon, Federica; Grassi, Gabriele
Aptamers as Targeting Delivery Devices or Anti-cancer Drugs for Fighting Tumors Journal Article
In: Current Drug Metabolism, vol. 14, no 5, pp. 565 - 582, 2013.
Abstract | Links | BibTeX | Tags:
@article{Scaggiante2013,
title = {Aptamers as Targeting Delivery Devices or Anti-cancer Drugs for Fighting Tumors},
author = {Bruna Scaggiante and Barbara Dapas and Rossella Farra and Mario Grassi and Gabriele Pozzato and Carlo Giansante and Nicola Fiotti and Elisa Tamai and Federica Tonon and Gabriele Grassi },
url = {http://www.eurekaselect.com/111247/article},
doi = {10.2174/13892002113149990010},
year = {2013},
date = {2013-01-01},
journal = {Current Drug Metabolism},
volume = {14},
number = {5},
pages = {565 - 582},
abstract = {Aptamer researches applied to the treatment of human cancers have increased since their discovery in 1990. This is due to different factors including: 1) the technical possibility to select, by SELEX-based procedures, specific aptamers targeting virtually any given molecule, 2) the aptamer favorable bio-activity in vivo, 3) the low production costs and 4) the ease synthesis and storage for the marketing. In the field of cancer treatments, aptamers have been studied as tumor-specific agents driving drugs into cancer cells; additionally they have been used as anti-neoplastic agents per se, able to inhibit tumor cell growth and dissemination when administered alone or in combination with conventional anti-neoplastic drugs. Aptamers are gaining an increased interest for pharmaceutical companies and some of them are under clinical evaluation trials.
In this review we update the findings about the use of aptamers as “escort" molecules able to drive drugs into the cells and as anti-neoplastic drugs per se. Current anti-neoplastic treatments suffer for the intrinsic toxicity related to the un-specific targeting of both normal and tumorigenic proliferating cells. The aptamers could be useful to improve: 1) the selective targeting of molecules essential for the viability and expansion of tumor cells and/or the selective driving of chemiotherapics into tumor cells, thus resulting in higher effectiveness and lower systemic side-effects compared to conventional anti-neoplastic drugs alone and 2) to improve the therapeutic index of currently used chemiotherapics. Even if some problems related to the in vivo stability and pharmacokinetic/dynamics of aptamers remain to be improved, their potential use in the treatment of different human cancers is getting closer and closer to a practical therapeutic use.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this review we update the findings about the use of aptamers as “escort" molecules able to drive drugs into the cells and as anti-neoplastic drugs per se. Current anti-neoplastic treatments suffer for the intrinsic toxicity related to the un-specific targeting of both normal and tumorigenic proliferating cells. The aptamers could be useful to improve: 1) the selective targeting of molecules essential for the viability and expansion of tumor cells and/or the selective driving of chemiotherapics into tumor cells, thus resulting in higher effectiveness and lower systemic side-effects compared to conventional anti-neoplastic drugs alone and 2) to improve the therapeutic index of currently used chemiotherapics. Even if some problems related to the in vivo stability and pharmacokinetic/dynamics of aptamers remain to be improved, their potential use in the treatment of different human cancers is getting closer and closer to a practical therapeutic use.
Coviello, Tommasina; Matricardi, Pietro; Alhaique, Franco; Farra, Rossella; Tesei, G.; Fiorentino, Simona Maria; Asaro, Fioretta; Milcovich, Gesmi; Grassi, Mario
Guar gum/borax hydrogel: Rheological, low field NMR and release characterizations Journal Article
In: Express Polymer Letters, vol. 7, no 9, pp. 733-746, 2013.
Abstract | Links | BibTeX | Tags:
@article{Coviello2013,
title = {Guar gum/borax hydrogel: Rheological, low field NMR and release characterizations},
author = {Tommasina Coviello and Pietro Matricardi and Franco Alhaique and Rossella Farra and G. Tesei and Simona Maria Fiorentino and Fioretta Asaro and Gesmi Milcovich and Mario Grassi},
url = {http://www.expresspolymlett.com/letolt.php?file=EPL-0004445\&mi=c},
doi = {10.3144/expresspolymlett.2013.71},
year = {2013},
date = {2013-01-01},
journal = {Express Polymer Letters},
volume = {7},
number = {9},
pages = {733-746},
abstract = {Guar gum (GG) and Guar gum/borax (GGb) hydrogels are studied by means of rheology, Low Field Nuclear Magnetic Resonance (LF NMR) and model drug release tests. These three approaches are used to estimate the mesh size (!) of the polymeric network. A comparison with similar Scleroglucan systems is carried out. In the case of GGb, the rheolog- ical and Low Field NMR estimations of ! lead to comparable results, while the drug release approach seems to underesti- mate !. Such discrepancy is attributed to the viscous effect of some polymeric chains that, although bound to the network to one end, can freely fluctuate among meshes. The viscous drag exerted by these chains slows down drug diffusion through the polymeric network. A proof for this hypothesis is given by the case of Scleroglucan gel, where the viscous contribution is not so significant and a good agreement between the rheological and release test approaches was found.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
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