Chitosan-TPP Nanogels for Foli Acid Ocular Delivery: Release Profile, Corneal Permeation, and Mucoadhesion Assessment

Folic acid (FA) is essential for cellular functions but has limited ocular bioavailability, which restricts its therapeutic effectiveness. This study developed chitosan-based nanogels (NG) as FA carriers, evaluating their mucoadhesion, drug release, and corneal permeation. Freshly prepared NGs had a hydrodynamic diameter of 312.4 ± 8.2 nm and a polydispersity index (PdI) of 0.28 ± 0.04, determined by Dynamic Light Scattering (DLS). FA encapsulation was confirmed through Fourier Transform Infrared (FTIR) spectros-copy, Differential Scanning Calorimetry (DSC), and Thermogravimetric Analysis (TGA). Scanning Electron Microscopy (SEM) revealed a uniform spherical morphology with minor variations in size and shape upon FA entrapment. Freeze-dried NG showed a 6.8% of size increase and PdI rise to 0.42, indicating aggregation within acceptable limits. In vitro drug release studies using a modified Franz diffusion cell demonstrated sustained FA release whose profile was fitted with Higuchi model. Mucoadhesion studies, carried out by ζ-potential measurements, revealed a decrease from +36.9 to +18.1 mV, confirming electrostatic interactions with mucin. Ex vivo corneal permeation in rabbits showed that encapsulated FA permeated 2.6 times slower than free FA, indi-cating sustained release. In conclusion, our findings demonstrate the potential of FA-loaded NG to enhance ocular drug delivery and bioavailability.