Eyes on the future: PVA-hydrogel lenses as a platform for amphotericin B ocular delivery

Ocular diseases, particularly infections such as fungal keratitis, present significant therapeutic challenges due to limited treatment options and low patient compliance. This study aimed to develop and characterize polyvinyl alcohol (PVA)-based hydrogel ophthalmic lenses (HOLs) incorporating amphotericin B (AmB) for potential use in treating fungal ocular infections. A central composite design (CCD) was employed to optimize the formulation, which was then evaluated for thickness, swelling degree, drug loading, release kinetics, and physicochemical properties via Fourier-transform infrared spectroscopy (FTIR), Powder X-ray diffraction (PXRD), and molecular dynamics simulations (MDS). Additional assessments included mass loss under physiological conditions (37 °C) and in vitro antifungal activity against clinical strains of Candida albicans, Candida parapsilosis, and Candida tropicalis. The CCD enabled precise mathematical modeling of swelling behavior, resulting in HOLs with controlled thickness (0.162 ± 0.011 mm to 0.265 ± 0.018 mm) and suitable hydration profiles. The results from FTIR and PXRD analyses confirmed effective crosslinking and indicated the presence of AmB in an amorphous or molecular dispersed state. After 30 days in artificial tear fluid (pH ∼ 7.4), the lenses exhibited low mass loss (4.4 ± 2.7%), supporting their structural stability. Release studies demonstrated a sustained and controlled AmB release profile, with cumulative release ranging from approximately 25% to 58% in the first 24 h among the tested formulations, consistent with the MDS findings that showed strong interactions between AmB, PVA, and sodium trimetaphosphate (STMP). The HOLs demonstrated antifungal efficacy, particularly against Candida parapsilosis. Overall, the developed PVA-based HOLs offer a promising platform for sustained ocular delivery of AmB in treatment of fungal infections.