Advances in Biodegradable Nano-Sized Polymer-Based Ocular Drug Delivery

Abstract

The effective delivery of drugs to the eye remains a challenge. The eye has a myriad of defense systems and physiological barriers that leaves ocular drug delivery systems with low bioavailability profiles. This is mainly due to poor permeability through the epithelia and rapid clearance from the eye following administration. However, recent advances in both polymeric drug delivery and biomedical nanotechnology have allowed for improvements to be made in the treatment of ocular conditions. The employment of biodegradable polymers in ocular formulations has led to improved retention time, greater bioavailability and controlled release through mucoadhesion to the epithelia in the eye, amongst other beneficial properties. Nanotechnology has been largely investigated for uses in the medical field, ranging from diagnosis of disease to treatment. The nanoscale of these developing drug delivery systems has helped to improve the penetration of drugs through the various ocular barriers, thus improving bioavailability. This review will highlight the physiological barriers encountered in the eye, current conventional treatment methods as well as how polymeric drug delivery and nanotechnology can be employed to optimize drug penetration to both the anterior and posterior segment of the eye.

Keywords: biodegradable; nanotechnology; ocular drug delivery; polymers.

Figure 1

Ocular physiological defenses that provide barriers for the delivery of drugs to segments of the eye, with each barrier highlighted, preventing drugs from penetrating across each membrane (Reprinted with permission from [13]).

Figure 2

Illustration of chitosan interaction with the mucin layer of corneal epithelium, allowing particle permeation via mucoadhesion [45].

Figure 3

Chemical structures of biodegradable polymers employed for ocular drug delivery. The natural polymers discussed are chitosan (a), hyaluronic acid (b), sodium alginate (c) and carboxymethylcellulose sodium (d). The synthetic polymers discussed are poly(lactic-co-glycolic acid) (e), poly(ɛ-caprolactone) (f) and poly(ethylene glycol) (g).

Figure 4

Poly(lactic-co-glycolic acid) polyethylene glycol (PLGA-PEG) nanoparticles, demonstrating greater mucin binding, employing lower density PEG coating compared to higher density, which decreases adhesion on the surface of mucin of the polymeric system (a). In vitro evaluation of PLGA-PEG nanoparticles, illustrating rapid diffusion in mucus ex vivo (b). Comparative analysis of commercial Loteprednol etabonate (LE) suspension eye drops to the polymeric delivery system in a New Zealand White (NZW) rabbit model, with almost 3-times greater Cmax profiles in rabbit aqueous humor, cornea and conjunctiva (c) (Reprinted with permission from [77]).

Figure 5

Illustration of hydrophobic drug entrapment within a chitosan nanoparticle, within a hydrophilic solvent environment [46].

Figure 6

Illustration of in situ gelling systems that could be delivered to the eye employing stimuli-responsive polymers as biodegradable drug delivery platforms [116].