Publications

@article{Caccavo2026,

title = {Process-guided design of nanoliposomal vitamin D3: formulation, stability and quality by design mapping},

author = {Diego Caccavo and Luca Broegg and Gaetano Lamberti and Raffaella De Piano and Anna Angela Barba},

url = {https://www.sciencedirect.com/science/article/pii/S0378517326002735/pdfft?md5=638132f36776e3d30c7e88f84953e514\&pid=1-s2.0-S0378517326002735-main.pdf},

doi = {https://doi.org/10.1016/j.ijpharm.2026.126825},

year  = {2026},

date = {2026-05-05},

urldate = {2026-05-05},

journal = {International Journal of Pharmaceutics},

volume = {696},

abstract = {The development of aqueous vitamin D3 supplements remains challenging because the molecule is poorly soluble, chemically fragile, and prone to loss of potency during storage. In this work, we adopted a Quality-by-Design (QbD) strategy to construct a nanoliposomal structure able to protect and deliver vitamin D3 while maintaining technological simplicity and high tolerability. As a first step, drug-free nanoliposomes were produced using a coaxial-jet mixer and systematically investigated through a Box\textendashBehnken Design. This approach allowed us to identify the critical relationships between phosphatidylcholine concentration, solvent/antisolvent flow rates, and the resulting nanoliposomal architecture, thereby defining a robust design space for nano-vesicle formation. Vitamin D3 was then introduced into the optimized system to verify process transferability. Encapsulation proved efficient and compatible with the micromixing-driven assembly of nanoliposomes, and the formulation was subsequently subjected to accelerated and real-time stability studies. These experiments revealed a clear hierarchy of stabilizing effects, highlighting the combined protective role of the liposomal bilayer and a carefully balanced antioxidant environment. Building on these findings, the research formulation was further refined into a commercially viable product, described in a dedicated patent, and benchmarked against leading marketed references. The final dispersion exhibited high structural uniformity, stable vitamin retention and manufacturing features consistent with large-scale implementation. Overall, this work demonstrates how a QbD-guided pathway \textemdash from mechanistic process mapping to stability-driven optimization and product translation \textemdash can yield a high-quality nanoliposomal vitamin D3 with clear technological and practical advantages.},

keywords = {Box\textendashBehnken design, Coaxial-jet mixing, nanoliposomes, Quality-by-Design, Vitamin D3},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2026d,

title = {Coaxial Jet Mixing for Pharmaceutical Nanocarrier Production: Experimental Analysis and Mechanistic Modeling},

author = {Diego Caccavo and Raffaella De Piano and Francesca Landi and Gaetano Lamberti and Anna Angela Barba},

url = {https://www.mdpi.com/1999-4923/18/4/507/pdf?version=1776679118},

doi = { 10.3390/pharmaceutics18040507 },

year  = {2026},

date = {2026-04-20},

journal = { Pharmaceutics},

volume = {18},

issue = {4},

abstract = {This study addresses the need for scalable and predictive strategies linking mixing conditions to nanocarrier properties by developing and analyzing a coaxial jet antisolvent process for the continuous production of pharmaceutical nanocarriers. Methods: A single experimental platform was used to generate both curcumin-based nanoparticles and nanoliposomes, enabling direct comparison of how mixing regime and formulation variables influence product characteristics. Results: Fluid-dynamic behavior was first characterized using tracer and micromixing experiments, revealing a strong dependence of mixing time on flow conditions, with characteristic mixing times decreasing from \>1000 ms under laminar conditions to approximately 10\textendash30 ms in turbulent regimes. Nanoparticles and liposomes obtained under optimized conditions exhibited mean sizes in the range of 120\textendash250 nm, with polydispersity indices typically below 0.2 under optimized turbulent conditions. To rationalize these observations, a computational framework was implemented, combining Reynolds-averaged computational fluid dynamics with a population balance formulation solved by the method of moments. The model provided spatially resolved insight into solvent exchange, supersaturation development, and nucleation\textendashgrowth dynamics, showing good agreement with experimental trends and capturing the effect of mixing conditions on particle size across different regimes. Conclusions: Although simplified, the modeling approach establishes the basis for future extensions toward full population-balance distribution simulations capable of predicting complete particle size distributions, highlighting the ability of the coaxial jet mixer to control supersaturation and particle formation through tunable hydrodynamic conditions. This capability makes the system particularly attractive compared to conventional batch or less controllable mixing technologies, enabling a more rational and scalable design of pharmaceutical nanocarriers, with good encapsulation performance as discussed in the main text.},

keywords = {antisolvent precipitation, coaxial jet mixer, computational fluid dynamics, modelling, nanoliposomes, population balance},

pubstate = {published},

tppubtype = {article}

}

@article{Lamberti2026,

title = {Fabrication and Characterization of Nerolidol-Based Invasomes: Loading, Stability and Antimicrobial Applications},

author = {Gaetano Lamberti and Raffaella De Piano and Diego Caccavo and Sara Guarino and Lorenzo Bosio and Dante Greco and Clotilde Silvia Cabassi and Nicol. Mezzasalma and Costanza Spadini and Federico Righi and Marica Simoni and Susanna Bosi and Anna Angela Barba},

url = {https://www.mdpi.com/1999-4923/18/4/410/pdf?version=1774869875},

doi = {10.3390/pharmaceutics18040410},

year  = {2026},

date = {2026-03-27},

urldate = {2026-03-27},

journal = { Pharmaceutics },

volume = {18},

issue = {4},

abstract = {Nerolidol (NER) is a sesquiterpene alcohol with recognized antimicrobial potential, whose applications as a pure substance are limited by hydrophobicity, instability, and cytotoxicity. Invasomes, i.e., liposomes with terpene ingredients, offer a strategy to improve their delivery; however, the NER loading limits compatible with vesicle integrity are still unclear. Here, Nerolidol-loaded invasomes were produced using a controlled simil-microfluidic coaxial injection process. Methods and Results: As a preliminary step, unloaded liposomes were fabricated to consolidate operating conditions and ensure their reproducible colloidal properties. Thereafter, formulations with progressively decreasing nominal NER loads were investigated to evaluate vesicle size, polydispersity, ζ-potential, encapsulation efficiency, effective loading, and stability. High nominal loads promoted turbidity, size increase (by agglomeration coalescence phenomena), and structural instability, whereas formulations containing approximately 1\textendash2% NER achieved nearly complete encapsulation, Z-average ≈ 300 nm, |ζ| \> 30 mV, and satisfactory physical stability. Antimicrobial and cytotoxic profiles of representative formulations, previously evaluated in an independent study are here reported only to contextualize the practical relevance of the optimized systems, while the present work primarily focuses on process\textendashformulation aspects and loading/stability limitations. Conclusions: Overall, the present work identifies a realistic loading window for Nerolidol invasomes and highlights the suitability of the simil-microfluidic approach to obtain scalable, well-controlled formulations, providing a rational basis for their future biological assessment. Nerolidol invasome systems indeed can be considered a promising, versatile platform for antimicrobial applications, including prospective use in animal feed.},

keywords = {antimicrobic activity, Invasomes, nanoliposomes, Nerolidol, simil-microfluidic technology},

pubstate = {published},

tppubtype = {article}

}

@article{Bochicchio2020,

title = {Simil-Microfluidic Nanotechnology in Manufacturing of Liposomes as Hydrophobic Antioxidants Skin Release Systems},

author = {Sabrina Bochicchio and Annalisa Dalmoro and Veronica {De Simone} and Paolo Bertoncin and Gaetano Lamberti and Anna Angela Barba},

url = {https://www.mdpi.com/2079-9284/7/2/22/pdf},

doi = {10.3390/cosmetics7020022},

year  = {2020},

date = {2020-04-03},

urldate = {2020-04-03},

journal = {Cosmetics},

volume = {7},

number = {22},

pages = {13},

abstract = {Novel nanotechnologies represent the most attractive and innovative tools to date exploited by cosmetic companies to improve the effectiveness of their formulations. In this context, nanoliposomes have had a great impact in topical preparations and dermocosmetics, allowing the transcutaneous penetration and absorption of several active ingredients and improving the stability of sensitive molecules. Despite the recent boom of this class of delivery systems, their industrial production is still limited by the lack of easily scalable production techniques. In this work, nanoliposomes for the topical administration of vitamin D3, K2, E, and curcumin, molecules with high antioxidant and skin curative properties but unstable and poorly absorbable, were produced through a novel simil-microfluidic technique. The developed high-yield semi continuous method is proposed as an alternative to face the problems linked with low productive conventional methods in order to produce antioxidant formulations with improved features. The novel technique has allowed to obtain a massive production of stable antioxidant vesicles of an 84\textendash145 nm size range, negatively charged, and characterized by high loads and encapsulation efficiencies. The obtained products as well as the developed high-performance technology make the achieved formulations very interesting for potential topical applications in the cosmetics/cosmeceutical field. },

keywords = {antioxidants, cosmeceutics, nanoliposomes, simil-microfluidic technology, transdermal delivery},

pubstate = {published},

tppubtype = {article}

}