Development and biopharmaceutical assessment of formulations for ocular and pulmonary drug delivery: application of mucoadhesive chemical entities, repurposing of drugs for ARDS and infection treatments

Topical administration is an easily accessible and highly compliant route of administration, optimal for local treatments and may be useful for non-invasive delivery of systemic drugs. Ocular diseases may be treated via different routes of administration, such as topical, intracameral, intravitreal, oral and parenteral. Among them the topical route is most accepted by patients, although it provides in many cases the lowest bioavailability. Differently, pulmonary delivery is adopted either for locoregional treatments of lung pathologies or for systemic absorbance of drugs, thanks to its extensive surface area, high vascularization, and a thin blood-alveolar barrier. Mucus often serves as a habitat for both commensal and pathogenic microorganisms. Consequently, mucosal surfaces are essential targets for local antimicrobial treatments and non-invasive drug delivery. However, due to its barrier properties, mucus poses challenges by hindering the diffusion and permeation of drugs, thereby affecting their local effectiveness and bioavailability. Enhancing ocular bioavailability involves extending ocular residence time, while in the context of lung delivery, optimizing the aerodynamic properties of the formulation is of great significance, as well as drug prompt solubility. In both scenarios, adherence to established guidelines is essential to ensure the stability, efficacy, and safety of the final product. The principal aim of this Ph.D. thesis is to develop excipients and formulations that improve either topical ocular drug delivery or enable drug efficacy upon inhalation.