Nanocarriers for ocular drug delivery: current status and translational opportunity

Abstract

Ocular diseases have a significant effect on vision and quality of life. Drug delivery to ocular tissues is a challenge to formulation scientists. The major barriers to delivering drugs to the anterior and posterior segments include physiological barriers (nasolacrimal drainage, blinking), anatomical barriers (static and dynamic), efflux pumps and metabolic barriers. The static barriers comprise the different layers of the cornea, sclera, and blood-aqueous barriers whereas dynamic barriers involve conjunctival blood flow, lymphatic clearance and tear drainage. The tight junctions of the blood-retinal barrier (BRB) restrict systemically administered drugs from entering the retina. Nanocarriers have been found to be effective at overcoming the issues associated with conventional ophthalmic dosage forms. Various nanocarriers, including nanodispersion systems, nanomicelles, lipidic nanocarriers, polymeric nanoparticles, liposomes, niosomes, and dendrimers, have been investigated for improved permeation and effective targeted drug delivery to various ophthalmic sites. In this review, various nanomedicines and their application for ophthalmic delivery of therapeutics are discussed. Additionally, scale-up and clinical status are also addressed to understand the current scenario for ophthalmic drug delivery.

Fig. 1. Schematic representation of the anatomy of the eye and physiological barriers to ocular drug delivery (red colour indicates the ocular diffusional barriers whereas green colour indicates routes of elimination). The cornea is the main route for drug penetration on topical administration (1). The conjunctival and scleral route allows some hydrophilic drugs, which further diffuse into the ciliary body (2). Following systemic administration, small compounds diffuse from the iris blood vessels into the anterior segment (3). Further, the drugs in the anterior segment are removed via aqueous humor outflow (4) or diffuse across the iris surface via venous blood flow (5). The retinal pigment epithelium and the retinal capillary endothelium act as major barriers to systemically administered drugs reaching the retina and vitreous humour (6). Instead of these, for effective drug delivery intravitreal injections are used (7). Drugs are removed from the vitreous humour via the blood–retinal barrier (8) or by diffusion into the anterior chamber (9). Reproduced with permission from ref. 17. Copyright 2005, Elsevier.

Fig. 2. Schematic representation of the routes of administration for ocular drug delivery.

Fig. 3. Schematic representation of different nanocarrier systems and their targeting ability. The permeation of nanomedicines across the ocular barrier on topical administration for the treatment of eye diseases. The symbols next to the nanocarriers in each layer of the eye indicate the targeting or permeation capability of the respective nanocarriers.

Fig. 4. Key components in the stages of product development, starting from preformulation (lab scale) to commercialization (production scale).