Engineered nanofibrous membrane as an in-vitro corneal model for drug permeation studies

Most ophthalmic drugs are administered topically due to ease of application, formulation versatility, and patient compliance. However, less than 10 % of the applied dose reaches the posterior segment, primarily due to the diffusional barrier of the corneal epithelium. Conventional permeability assessments rely on excised animal corneas, which not only raise ethical concerns but also suffer from poor reproducibility and limited correlation to human physiology. To address these limitations, a bioinspired reverse slippery liquid-infused porous surface (r-SLIPS) membrane was developed as a novel in-vitro corneal model for passive drug diffusion. A freestanding, self-assembled phosphatidylcholine (PC)-infused electrospun polystyrene (PS) nanofibrous membrane, termed the biomimetic lipid-polymer composite membrane (BLCM), was fabricated to emulate the multilayered architecture and amphiphilic surface of the native corneal epithelium. Morphological, spectroscopic, and wettability analyses confirmed homogeneous lipid distribution and hydrophilic surface chemistry. Permeation studies with hydrophilic (gentamicin sulphate), amphoteric (ciprofloxacin hydrochloride), and lipophilic (miconazole nitrate) model drugs revealed a strong correlation between apparent permeability and LogP, indicating a lipid-partition-driven diffusion mechanism. Dynamic light scattering (DLS) analyses demonstrated micelle- or vesicle-assisted transport across the membrane, with drug-lipid complex formation and disassembly occurring during permeation. Notably, the PC layer encapsulated lipophilic drugs into transient micellar structures, facilitating translocation across the nanofibrous scaffold. The resulting flux values corroborated with those obtained using excised goat corneas (p > 0.05). With excellent stability, scalability, and biomimetic performance, the BLCM offers an ethical, reproducible, and physiologically relevant platform for ocular drug permeability screening and early-stage pharmaceutical development.