DESIGN AND DEVELOPMENT OF A SUSTAINABLE MANUFACTURING PROCESS FOR THE PREPARATION OF ALBUMIN-BASED NANOMEDICINE ABLE TO CARRY LIPOPHILIC AND HYDROPHILIC MOLECULES

This PhD thesis presents an extensive investigation into the design, development and optimisation of albumin-based nanomedicines for drug delivery systems, with a particular focus on nanoparticles (NPs) and nanocapsules (NCs). Albumin, a biocompatible and biodegradable protein, was selected for its exceptional drug-binding properties, rendering it an optimal nanocarrier for therapeutic applications. The research primarily investigated two types of albumins: bovine serum albumin (BSA) and human serum albumin (HSA). The principal objective of the study was to develop albumin-based nanocarriers through the implementation of innovative and sustainable manufacturing processes. To develop nanocarriers with superior physicochemical characteristics, advanced technologies including surfactant-mediated coacervation, ultrasonication (US), microwave-assisted (MW), and combined microwave and ultrasonication (MW/US) were employed. These methods were optimised in order to meet specific quality target attributes, including particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, in vitro drug release profiles, and stability. This was done in accordance with the guidance set out in ICH Q8. The research was pivotal in the development of a more environmentally-conscious and sustainable manufacturing for the production of nanomedicines. The use of MW, US, and MW/US technologies, in the absence of organic solvents, has the dual benefit of reducing environmental impact and enhancing the efficiency of the production process. This innovation addressed both scientific and ecological challenges, offering a scalable, environmentally responsible pathway for the production of albumin nanomedicines. The encapsulation of doxorubicin hydrochloride, a well-known chemotherapeutic agent, into BSA and HSA nanocarriers was successfully achieved. These formulations demonstrated targeted delivery to cancer cells by modifying the surface of the nanocarriers with ICOS-Fc ligands, thereby enhancing receptor-mediated uptake. This targeted approach not only improved the therapeutic efficacy of doxorubicin but also minimized adverse side effects, showcasing the potential of these albumin-based systems in cancer treatment. The comparative analysis between BSA and HSA nanocarriers highlighted the adaptability of the optimized conditions. The formulations using BSA were effectively translated to HSA with minimal modifications, demonstrating the versatility and applicability of the process for nanomedicines. This work makes a significant contribution to the emerging field of nanomedicine, demonstrating that albumin-based nanocarriers can be produced using advanced, scalable, and sustainable technologies. The optimised formulations provide a template for future drug delivery systems, particularly in the context of cancer therapeutics, where targeted delivery and reduced toxicity are of paramount importance. The research establishes a robust foundation for the translation of these laboratory-scale innovations into large-scale production, ensuring consistent quality, safety, and efficacy in clinical applications. In conclusion, the study advances the understanding of albumin-based nanomedicine and demonstrates a practical, environmentally friendly approach to producing high-quality albumin-based drug delivery systems. This research holds promise for the future development of nanomedicines, with potential applications extending beyond cancer to other therapeutic areas.