Preparation and Evaluation of Ascorbyl Glucoside and Ascorbic Acid Solid in Oil Nanodispersions for Corneal Epithelial Wound Healing

The objective of this study was to develop and evaluate an effective topical formulation to promote corneal epithelial wound healing. Ascorbyl glucoside (AA-2G), a stable prodrug of AA, was formulated in solid in oil (S/ O) nanodispersions by emulsifying AA-2G solutions in cyclohexane using Span 85 as an emulsifying agent and freeze-drying emulsions to produce AA-2G - surfactant complex. The complexes were then dispersed in castor oil to produce S/O nanodispersions which were evaluated in terms of their particle size, polydispersity index, encapsulation efficiency, morphology, physical stability as well as the transcorneal permeation and accumulation of AA-2G. The same preparation procedure was used to prepare S/O nanodispersions of AA. S/O nanodispersions of AA and AA-2G were formulated into oily drops that were tested for efficacy in promoting wound healing after corneal epithelial depredation.AA-2G was loaded efficiently in S/O nanodispersions (EE > 99%) in the form of spherical nanoparticles. S/O nanodispersions were physically stable and resulted in improved permeation (18x) and accumulation (7x) of AA2G in transcorneal diffusion experiments in comparison to AA-2G solutions. Oily eye drops of AA-2G and AA showed no irritation and significant improvement in epithelial healing in vivo in comparison to AA-2G and AA solutions.