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

Abstract

Ocular drug delivery has been a major challenge for clinical pharmacologists and biomaterial scientists due to intricate and unique anatomical and physiological barriers in the eye. The critical requirement varies from anterior and posterior ocular segments from a drug delivery perspective. Recently, many new drugs with special formulations have been introduced for targeted delivery with modified methods and routes of drug administration to improve drug delivery efficacy. Current developments in nanoformulations of drug carrier systems have become a promising attribute to enhance drug retention/permeation and prolong drug release in ocular tissue. Biodegradable polymers have been explored as the base polymers to prepare nanocarriers for encasing existing drugs to enhance the therapeutic effect with better tissue adherence, prolonged drug action, improved bioavailability, decreased toxicity, and targeted delivery in eye. In this review, we summarized recent studies on sustained ocular drug/gene delivery and emphasized on the nanocarriers made by biodegradable polymers such as liposome, poly lactic-co-glycolic acid (PLGA), chitosan, and gelatin. Moreover, we discussed the bio-distribution of these nanocarriers in the ocular tissue and their therapeutic applications in various ocular diseases.

Keywords: anterior; biodegradable; drug/gene delivery; nanoparticles; ocular; polymeric; posterior.

Figure 1

Schematic diagram of the ocular structure with various ocular barriers. The ocular barriers in the anterior segment area (I) tear film and corneal epithelium, and (II) aqueous humor. The ocular barriers in the posterior segment are (III) sclera, (IV) choroid, and (V) vitreous humor. There are two BRBs. The blood–aqueous barrier in the anterior segment, a part composed of the non-pigmented ciliary epithelial cells and iris capillaries endothelial cells. The BRB, a tight-junction between non-fenestrated capillaries of the retinal blood circulation and retinal pigment epithelial cells in the posterior segment of the eye.

Figure 2

Methods of ocular drug administration and its delivery routes to the posterior segment. Routs of drug transportation to the back of the eye via topical administration (1 and 2), subconjunctival injection (3), subretinal injection (4), and intravitreal injection (5). The drug transportation from the systemic circulation via oral medication (6).

Figure 3

(I) Distribution of NPs with various surface properties in the different region of vitreous and retina via intravitreal injection. (II) Distribution of HSA NPs (red channel) in the retina via intravitreal injection. (A,D) Penetration of HSS NPs into the retina at 6 h post-injection, (E) scan of the whole retina, and (F) colocalization with Müller cells (green channel). ILM: inner limiting membrane, NFL: nerve fiber layer, GCL: ganglion cell layer, IPL: inner plexiform layer, INL: inner nuclear layer, OPL: outer plexiform layer, ONL: outer nuclear layer, PRL: photoreceptor layer, RPE: retinal pigment epithelium. Image adapted from Koo et al. (2012) and reprinted with permission from Biomaterials (Koo et al. 2012) [42].

Figure 4

Possible routes of drug delivery to the retina via topical administration. After topical instillation, NPs generally distribute through three main pathways: tear turnover, anterior (cornea/conjunctiva), and the nasolarimal drainage system. RPE: retinal pigment epithelium; BRB: blood–retinal barrier.