(287) Design and Development of Long-Term Therapy for Corneal Repair and Healing – ‘Nanoparticles-in-Dual-Gels’

Objective : We aimed to develop a dual-gel cocktail therapy that would fill the treatment gap with safety and patient adherence in lieu of invasive procedures for corneal wound management and self-healing. For this, PLGA-PPS-based nanoparticles (NPs)-loaded with dexamethasone (DEX), and rapamycin (RAPA) are embedded in the stimuli-responsive dual-gels assembly, that consists of thermo-responsive poloxamer (trPol) and photo-responsive gelatin methyl acrylate (prGelMa)- based hydrogels for long-term drug release. The dual gels create a natural microenvironment for self-repair and wound healing of cornea.

Methods: trPol and prGelMa polymers were synthesized for hydrogel formulation. The purified and freeze-dried trPol and prGelMa were characterized using 1H NMR. Several physicochemical parameters, like gel texture, photo-induced and sol-gel transitions were determined. NPs were prepared using nanoprecipitation method for DEX, and RAPA, and characterized for surface morphology, size, stability, entrapment, and loading efficiency using DLS, NTA, and TEM. The drug-loaded NPs were embedded in the trPol and prGelMa gel combination and characterized for in vitro release kinetics.

Results: 1H NMR of trPol and prGelMa confirmed the synthesis of hydrogels and photo-induced transition, sol-gel transition were performed. The size (nm)/ polydispersity index of the prepared DEX, and RAPA-NPs determined by DLS was found to be 105.2±0.2 /0.153±0.021, and 114.9±2.93/0.124±0.024, respectively. The NTA and TEM confirm their monodispersity, and spherical morphology. The encapsulation efficiencies of DEX, and RAPA, were found to be 87.27±2.15%, and 88.11±5.44%, respectively and NPs were found stable at 4°C storage for 6 months. The release kinetics of drugs were determined by the Korsmeyer-Peppas model suggests a non-Fickian diffusion mechanism (0.45< n < 1).

Conclusions: The drug-loaded NPs, stimuli-responsive hydrogels, and nanoparticles-in-dual-gels were successfully developed for a month-long therapy of corneal wound healing and repair.