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Ocular drug delivery

Severe vision loss from vitreoretinal (VR) diseases such as age-related macular degeneration (AMD), retinitis pigmentosa (RP), intraocular lymphoma (IOL), uveitis and proliferative retinopathy (PVR ) accounts for most cases of irreversible ocular diseases world-wide. Existing therapeutic procedures for treatment of VR diseases are limited as: 1) systemic drug therapy administered through mouth or injected into the bloodstream, and topical administration such as eye drops, fail to penetrate the physiological barriers; 2) intravitreal injections can lead to uneven drug distribution causing increased toxicity for non-target ocular tissues; and 3) in comparison to lipophilic (not water soluble) drugs, sustained release devices for hydrophilic (water soluble) drugs for treating VR diseases are difficult to fabricate, as these hydrophilic drugs do not bind well with existing FDA approved lipophilic materials.

At present, research is being conducted in developing a novel polymer-based biodegradable intravitreal micro-implant platform (Figure. 1) which administers therapeutic release of hydrophilic drug such as Methotrexate (MTX) over a period of more than 1 month. This study involves formulation and fabrication of the micro-implant drug delivery platform along with the in-vitro material characterization and pharmacokinetics analysis. The micro-implant has been further evaluated in vivo, in a limited number of rabbit eyes where it showed therapeutic release of the drug for > 1 month without any evidence of toxicity.

occular drug delivery_fig 1
Figure 1. Intravitreal micro-implant

In the recent past our group has also conducted several numerical studies which included a) development of a 3D finite element eye model to compare the pharmacokinetics of drug distribution between an intravitreal injection and a sustained release device, b) evaluating the influence of drug transport parameters such as retinal permeability, drug diffusivity and hydrodynamic conditions within the VR domain of the eye, and c) determining the optimal range of sustained drug release for therapeutic efficacy to treat VR diseases.

Our group has also carried out ex vivo studies related to ocular drug delivery where, the therapeutic efficacy 2-Methoxyestradiol (2ME2), a potential antitumor agent with minimal toxicity, was assessed in relation to MTX, for treating lymphoma using Farage and Pfeiffer cell lines.

The above research has been conducted in collaboration with Department of Ophthalmology resulting in 7 journal publications and 1 patent.

by zopeown last modified 2015-05-18 18:02