Effect of liposomal formulation of ascorbic acid on corneal permeability

Abstract

Ascorbic acid (AA) has a pivotal role in corneal wound healing via stimulating the biosynthesis of highly organized extracellular matrix components, but its rapid degradation and low corneal permeability limits its therapeutic effects. In this paper, we present the pharmacokinetic properties of a liposomal-based formulation of AA in terms of corneal permeation. Chemical stability, shelf-life, and drug release rate of lyophilized liposome (AA-LLipo) formulation was determined in comparison to free-form of AA solution using high-performance liquid chromatography (HPLC) and rapid equilibrium dialysis. In vitro transcorneal permeability was studied using a parallel artificial membrane permeability assay (PAMPA). Ex vivo permeation was examined on AA-LLipo-treated porcine cornea by determining the AA content on the ocular surface, in the cornea as well as in the aqueous humor using HPLC, and by Raman-mapping visualizing the AA-distribution. Our results showed that the liposomal formulation improved the chemical stability of AA, while drug release was observed with the same kinetic efficiency as from the free-form of AA solution. Both corneal-PAMPA and porcine corneal permeability studies showed that AA-LLipo markedly improved the corneal absorption kinetics of AA, thus, increasing the AA content in the cornea and aqueous humor. AA-LLipo formulation could potentially increase the bioavailability of AA in corneal tissues.

Dendritic Oligoethylenimine Decorated Liposome with Augmented Corneal Retention and Permeation for Efficient Topical Delivery of Antiglaucoma Drugs

“…Free latanoprost is more efficient at crossing the cornea as 16.4% of the drug permeated through the cornea in 4 h, which is 10-fold higher than free timolol (Figure b, c). Since the corneal epithelium and endothelium are hydrophobic, the penetration through the cornea is more favored for lipophilic drugs compared with hydrophilic drugs, which greatly limits the penetration of hydrophilic drugs into the anterior chamber and is the main barrier for water-soluble drugs to enter the eye . By using PL as the drug delivery vehicle, the corneal transport for both timolol and latanoprost is promoted significantly.…”

“…Since the corneal epithelium and endothelium are hydrophobic, the penetration through the cornea is more favored for lipophilic drugs compared with hydrophilic drugs, which greatly limits the penetration of hydrophilic drugs into the anterior chamber and is the main barrier for water-soluble drugs to enter the eye. 54 By using PL as the drug delivery vehicle, the corneal transport for both timolol and latanoprost is promoted significantly. Within 4 h, 3% of timolol from TPL and 22% of latanoprost from LPL pass through the cornea, respectively, which is 2-fold and 1.4-fold higher than their respective free drugs.…”