Nanocarriers and crosslinked films for the ocular delivery of neuroprotective compounds

This Ph.D. project aimed to develop innovative formulation strategies to improve the ocular delivery of hydrophobic neuroprotective drugs. The main goal was to overcome the anatomical and physiological barriers that limit drug access to the retina and to design systems able to provide controlled and sustained release. Two types of nanocarriers based on a hydrophilic derivative of vitamin E (TPGS, D-a-tocopheryl polyethylene glycol succinate) were prepared and studied: TPGS-based micelles and TPGS-functionalized liposomes. Both systems improved the solubility and stability of poorly soluble drugs and the results highlighted the significant impact of PEG chain length on the nanocarrier properties. For instance, TPGS 1000 micelles showed the best balance between stability, drug loading, and diffusion, while TPGS 600 proved to be the most suitable derivative for liposomes functionalization, obtaining system with high flexibility and reduced drug leakage, supporting their potential for ocular delivery. TPGS micelles were then incorporated into crosslinked polymeric films to obtain a platform capable of controlled and prolonged drug release. The films preserved the nanocarriers’ properties, ensured good biocompatibility, and allowed the sustained delivery of the loaded drugs. The same platform was also adapted as a wound dressing for localized antibacterial therapy, demonstrating its versatility. Overall, this work shows that combining nanocarriers with crosslinked polymeric films can lead to multifunctional systems suitable for the controlled and localized delivery of hydrophobic drugs to the eye and other tissues.