Dottorato in SCIENZE FARMACEUTICHE

Titolo della tesi: Innovative strategies for the development of biopolymer-based materials with suitable properties for biomedical and pharmaceutical applications

The purpose of the present research work has been to investigate innovative approaches to expand the application of biopolymer matrices in biomedical and pharmaceutical fields. In particular, the focus has been on polymer thin films and hydrogels and their current use as drug delivery systems, wound dressings, and tissue engineering scaffolds. Based on its film-forming properties, gellan gum was chosen to produce polymer thin films, both in its unmodified form and after a suitable chemical modification, in an effort to address some of the major issues that could arise during the development of these formulations, which mainly concern the drug-loading capacity, bioadhesion, and incorporation of silver nanoparticles (AgNPs). In the specific, the strategies proposed involved the addition of hydroxypropyl-β-cyclodextrin in films based on non-derivatized GG to prevent the crystallization of a model BCS I drug (fluconazole). Instead, the derivatization of GG carboxyl groups with dopamine (GGDA) was explored as a semi-synthetic approach for mimicking marine-inspired bioadhesion processes. Finally, a methacrylate derivative of GG (GG-MA) was used to produce through UV irradiation and in a single manufacturing step, thin nanocomposite films containing AgNPs. Hydrogels are considered the biomaterials that most closely resemble natural living tissues. However, the small pore size and low interconnectivity has been found to be inadequate for cell growth and proliferation. An improvement can be achieved by using the technique known as "cryogelation". To promote cell recognition and adhesion, which are essential for mimicking the biological functions of the natural ECM, dextran methacrylate (DexMA) was combined with the methacryloyl derivative of gelatin (GelMA) produced following an innovative single-phase synthetic protocol and characterized by a very low gelation temperature. Therefore, cryogels were developed through radical polymerization of the methacrylate derivatives performed using APS/TEMED as radical crosslinking agents. The polymeric composition of the matrices was varied and its effect on the internal structure of the resulting systems was evaluated.