Preparation and evaluation of ascorbyl glucoside and ascorbic acid solid in oil nanodispersions for corneal epithelial wound healing

Int J Pharm. 2022 Nov 5:627:122227. doi: 10.1016/j.ijpharm.2022.122227. Epub 2022 Sep 23.

Abstract

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 AA-2G 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.

Keywords: Ascorbyl glucoside; Corneal epithelial debridement; Hydrophobic nanoparticles; Ophthalmic drug delivery; Solid in oil nanodispersions; Vitamin C.

MeSH terms

  • Ascorbic Acid
  • Castor Oil
  • Corneal Injuries*
  • Cyclohexanes
  • Emulsifying Agents
  • Glucosides
  • Humans
  • Ophthalmic Solutions
  • Prodrugs*
  • Surface-Active Agents
  • Wound Healing

Substances

  • ascorbic acid 2-O-glucoside
  • Castor Oil
  • Prodrugs
  • Ascorbic Acid
  • Ophthalmic Solutions
  • Surface-Active Agents
  • Emulsifying Agents
  • Cyclohexanes
  • Glucosides