Progress in the design of chitosan-based nanogels for folic acid delivery for ocular applications

Folic acid (FA) plays a vital role in cellular metabolism, DNA and RNA synthesis, and antioxidant defences. However, FA's bioavailability is limited due to its susceptibility to environmental agents and physiological conditions, making essential an effective protection system. In this context, Nanogels (NG) were developed for FA ophthalmic delivery using ionic gelation with chitosan (CS) and tripolyphosphate (TPP) in different mass ratios. The optimized formulation, selected based on experimental design, consisted of 2.25 mg/mL CS and 0.75 mg/mL TPP. For an initial FA concentration of 300 μM, the encapsulation efficiency was 81%. NG FA-300 formulation displayed a monodisperse size of 222 nm, low polydispersity (0.30), and a ζ-potential of +24.9 mV. TEM and AFM analyses showed spheroid particles with low height with rough surface. In vitro release profile of FA from the NG described a first-order kinetics under simulated tear fluid. ABTS assays confirmed that FA retained antioxidant activity within the NG. Biocompatibility tests showed no cytotoxicity to ARPE-19 cells, with efficient internalization visualized by FITC-NG and avoidance of endo-lysosomal degradation. FA into NG did not alter its biological activity and helped to mitigate oxidative stress in cells. CS NG are promising vehicles for FA delivery for ocular applications.