Giorgio Buttitta
| Liposomes: the gold standard in drug delivery technology |
| Buttitta Giorgio1, Luciani Paola2, Bonacorsi Simone1,3, Barbarito Chiara3, Moliterno Mauro3, Pompei Simona3, Saito Gabriele3, Oddone Irene3, Verdone Giuliana3, Raimondi Sergio3, Guglielmi Paolo1 and Secci Daniela1 1 Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy 2 Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland 3 BSP Pharmaceuticals S.p.A., Via Appia Km. 65,561, 04013 Latina Scalo (LT), Italy. |
| Abstract Liposomes are phospholipid vesicles able to encapsulate hydrophilic and hydrophobic compounds, enabling controlled drug delivery with high biocompatibility and clinical relevance. This industrial PhD thesis investigates advanced liposomal drug delivery systems through three interconnected projects focused on sustained release, formulation optimization, and scalable manufacturing. The first project, conducted at the University of Bern, addressed the limitations of carprofen, a poorly soluble nonsteroidal anti-inflammatory drug used in veterinary medicine. A depot liposomal formulation was developed to achieve prolonged release after subcutaneous administration. Formulation screening and physicochemical characterization enabled optimization of the system, while an agarose gel matrix model simulating the subcutaneous environment was designed to evaluate sustained-release behavior in vitro. Preliminary scale-up demonstrated translational potential. The second project focused on lipid-based carriers for neurodegenerative disease treatment. A human monoamine oxidase B inhibitor was incorporated into highly PEGylated liposomes. Using Design of Experiments combined with microfluidics, critical process parameters were optimized to obtain formulations with controlled quality attributes, demonstrating the value of integrating medicinal chemistry, nanotechnology, and formulation science. The final project, carried out at BSP Pharmaceuticals, established a scalable microfluidic platform for liposome manufacturing. Commercial-like formulations inspired by Doxil® and Marqibo® were reproduced and optimized, generating highly monodisperse and regulatory-compliant liposomes. The platform enabled rapid scale-up, producing up to 1 L of formulation in less than 20 min. Overall, this thesis demonstrates how rational formulation design, microfluidic technologies, and scalable manufacturing can advance liposomal nanomedicine from laboratory research to industrial production. |