Cationic Gelatin Nanoparticles for Drug Delivery to the Ocular Surface: In Vitro and In Vivo Evaluation

Abstract

To develop an effective ocular drug delivery carrier, we prepared two different charged gelatin nanoparticles (GPs) and evaluated particle size, surface charge, and morphology. The in vitro biocompatibility of GPs was assessed using human corneal epithelium (HCE) cells and in vivo safety by administering them as eye drops to New Zealand rabbits. The GPs prepared using type A gelatin were positively charged (GP(+), +33 mV; size, 180.6 ± 45.7 nm). Water-soluble tetrazolium salt (WST)-1 assay showed that both GPs were nontoxic to HCE cells. The fluorescence intensity of HCE cells cultured with cationic GPs conjugated with a fluorescent dye was higher than that of the anionic GP-treated HCE cells. In vivo examination showed no serious irritation to the rabbit eyes. Furthermore, corneal thickness and ocular pressure in the eyes of the treated rabbits were similar to those in the eyes of normal rabbits. Microscopic examination of corneal cryosections showed widely distributed fluorescent nanocarriers, from the anterior to the posterior part of the cornea of the GP(+) group, and higher fluorescence intensity in the GP(+) group was also observed. In conclusion, GPs as cationic colloidal carriers were efficiently adsorbed on the negatively charged cornea without irritating the eyes of the rabbits and can be retained in the cornea for a longer time. Thus, GPs(+) have a great potential as vehicles for ocular drug delivery.

Preparation of arginine–glycine–aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization

“…36 Our previous study showed that cationic gelatin NPs (GNPs) can be attracted to rabbit cornea and retained in the cornea for a longer time. 38 Therefore, GNPs with positive charge are promising as vehicles for ocular drug delivery.…”

Ocular Drug Delivery: Role of Degradable Polymeric Nanocarriers for Ophthalmic Application

“…For instance, the cornea and conjunctiva possess negative surface charges, and it is expected that the cationic colloidal NPs can enhance the retention time on negatively charged ocular tissues more efficiently than the anionic carriers, providing an increased opportunity for the drug to enter the eye [ 37 ]. Tseng et al 2013, proved that the topical administration of positively charged gelatin nanoparticles could prolong the drug retention time on the negatively charged ocular surface, compared to the free-form drug formulation [ 38 ]. Xu et al 2013, found that NPs coated with different surface charges of polyethylene glycol (PEG) resulted in a variant delivery efficacy in an ex vivo model of the bovine vitreous body.…”

Therapeutics and Carriers: The Dual Role of Proteins in Nanoparticles for Ocular Delivery

“…Thanks to the high biocompatibility shown, several examples of gelatin NPs intended for ophthalmic use can be found in the literature. Gelatin allows the preparation of both positive and negative NPs, with smooth surface and spherical shape [97], to be administered either topically [97,98] or intra-vitreally [68] and loaded with small molecules [98] as well as with high molecular weight compounds [68]. In order to increase ocular bioavailability of pilocarpine HCl and hydrocortisone, two drugs with different solubility, they were encapsulated in gelatin NPs via desolvation method [98].…”

“…Since the ocular surface is negatively charged, because of the presence of sialic acid residues in the mucus, some authors suggested that cationic NPs may better interact and/or penetrate cornea and conjunctiva than the anionic ones [97,99]. For this reason, cationic gelatin NPs were prepared and loaded with a plasmid designed to encode human MUC5AC [100].…”