(176au) Investigating the Impact of a Nanocarrier Physiochemical Properties on Penetration into Ocular Surface Barriers

Visual impairment is a global health concern and the number of people dealing with visual impairment and blindness is increasing globally. So there is a growing demand for strategies improving ocular disease treatment and nanotechnology seems to be one of the most promising approaches that has been applied in several studies during the past couple of years to investigate potential improvement to ocular disease treatment either by enhancing biocompatibility and bioavailability or by providing controlled release, targeted therapy, and low toxicity.

Ocular diseases can be treated by several routes including topical, intraocular, and systemic administration. Among these administration routes, topical instillation is the least invasive, most dominant self-administrable route for treatment of ocular diseases. Currently, more than 90% of ophthalmic formulations in the market are in the forms of eye drops. However, the bioavailability of the drugs that are applied topically is very low ranging between 0.001%- 5% depending on the target site from the anterior segment of the eye to the posterior segment. The low ocular bioavailability of topically applied drugs are due to the unique structure of the eye with several anatomical and physiological barriers that statically and dynamically limit drugs absorption into the eye. These barriers include tear film, cornea, and conjunctiva which are considered as anterior barriers located on the surface of the eye and also blood-aqueous barrier and blood-retinal barrier which are considered as posterior barriers located inside the eye ball.

To treat any ocular disease by topical instillation which is the administration route of interest in this research, the main challenge is successful transport of therapeutic agent into the eye ball by overcoming the ocular surface barriers which are mainly composed of mucosal and epithelial components. Transport of therapeutic agent into the eye is influenced by two general factors: ocular barriers properties including their physiological structure and functional behavior and also nanocarrier properties including their size, morphology, and surface properties. To design an ideal drug delivery system for a particular application, it is desired to tune the physiochemical properties of the therapeutic agent based on the requirement of that specific application. Hence, the ultimate goal of this study is to gain knowledge of the interplay between the nanocarrier and ocular surface barriers to understand how to address the penetration issue that restricts the therapeutic agent to reach to the target site. The significance of this research is to develop an in vitro and an ex vivo models for ocular surface barriers mimicking mucosal and epithelial barriers closely integrated together similar to in vivo condition and investigate how manipulation of physiochemical properties of nanocarrier would improve the nanocarrier penetration into the eye.

The nanocarrier under study in this work is a polymeric based nanoparticle made of poly lactic-co-glycolic acid or PLGA which is being engineered in different sizes and surface functionalized with different mucoadhesive, mucopenetrative, and combined mucopenetrative-cell penetrative agents to investigate the effect of size and surface properties on penetration into ocular surface barriers.