Brimonidine formulation in polyacrylic acid nanoparticles for ophthalmic delivery

Abstract

In ocular drug delivery, a major problem is providing an adequate concentration of a therapeutic agent in the precorneal area. Mucoadhesive carriers such as polyacrylic acid in sub-colloidal, nanoparticulate form, have a strong potential for ophthalmic drug delivery. A formulation of brimonidine loaded in polyacrylic acid nanoparticles has been prepared for potential delivery in ophthalmic therapy. The particles were prepared by a reverse microemulsion polymerization technique and their sizes were in the range of 50 nm. In a preliminary biocompatibility test, Caco-2 cells (human primary colonic tumour adenocarcinoma) and human corneal epithelial cells incubated with polyacrylic acid nanoparticles were found to retain their viability over varying times. The loading efficiency of the drug brimonidine in the particles was shown to be between 80-85% and pH dependent. The bioadhesive polyacrylic hydrogel nanoparticles, used in the present study, exhibited superior loading properties for brimonidine, and the formulation was stable for more than 5 weeks. When the drug-loaded nanoparticles were dispersed in a phosphate buffer saline (pH = 7.4), the drug was slowly released over several hours. Two-photon laser scanning microscopic studies of dye-conjugated polyacrylic acid nanoparticles demonstrated the accumulation of the particles on the surface and intercellular spaces of Caco-2 cells.

Review of Ocular Drug Delivery

“…De et al prepared and evaluated brimonidine loaded polyacrylic acid nanoparticles for potential delivery in ophthalmic therapy. The bioadhesive polyacrylic hydrogel nanoparticles, used in the present study, exhibited superior loading properties for brimonidine, and the formulation was stable for more than 5 weeks [69].…”

A Nonionic Surfactant/Chitosan Micelle System in an Innovative Eye Drop Formulation

“…Although Caco-2 cells are of intestinal origin, they have been used to study more general membrane effects of drug delivery systems intended for ocular administration. [31][32][33] Figure 2 shows the results of the transport studies of DEX from the F127/CH micelle systems across Caco-2 cell monolayers at pH 4.5. The duration of the DEX transport experiments was 3 h, because a longer retention of delivery systems at the ocular surface cannot be expected due to precorneal loss factors.…”

Polycarboxylic acid nanoparticles for ophthalmic drug delivery: anex vivoevaluation with human cornea

“…Brimonidine-loading was performed as previously described (De et al 2003). Brimonidine (0.5-2.6 mg) was transferred to 1.5 ml micro-centrifuge tubes containing 5 mg of PAA nanoparticles or PIA nanoparticles in 1.0 ml of water.…”

“…Mucoadhesion is an important feature of topical sustained-release dosage forms which may increase the duration or intensity of contact between drug molecules and the epithelium, thus provide control over the site and duration of drug release (Park and Robinson 1987, Gu et al 1988, Thermes et al 1992a, b, BlancoFuente et al 1996, Peppas and Sahlin 1996, Ahuja et al 1997, Genta et al 1997, Jones et al 1997, Tur and Chang 1998, De et al 2003. Thermes et al (1992b) have shown that the mucoadhesive polymer, PAA, modified the kinetic release profiles of timolol in the albino rabbit eye.…”

“…The nanoparticulate form of a mucoadhesive polymer, like PAA in colloidal suspension, has been recognized as a strong potential carrier for ocular delivery. A formulation of brimonidine loaded in PAA nanoparticles was recently developed as a potential delivery vector for ophthalmic applications (De et al 2003). Brimonidine (figure 1) is a highly selective 2 -adrenoceptor agonist that has markedly greater affinity for 2 -adrenoceptors than apraclonidine (23-32 fold) and clonidine (6-12 fold) (Munk et al 1995, Burke et al 1996.…”