Development of new carriers to improve the bioavailability of natural compounds to treat ocular surface disorders

Abstract

Polyphenols constitute one of the most widespread class of compounds throughout the plant kingdom. Among them, quercetin (QUE) and resveratrol (RSV) emerge for their extraordinary beneficial health effects. Although widely studied, currently there are no commercially available formulations of these compounds.Given their extensive potential in the treatment of diverse health disorders , including ones related with the ocular surface , the main goal of this thesis was the development of formulations capable of circumventing the physico-chemical limitations (such as poor aqueous solubility and low chemical stability) that the two molecules possess. Moreover, an advanced formulation strategy will help overcome the physiological and anatomical barriers related to the targeted tissues in the ocular surface. Four different formulations were studied for the topical ophthalmic delivery of QUE and RSV. Two of them, inclusion complexes with cyclodextrins and elastin-like recombinamer nanoparticles displayed promising results. These formulations were capable of positively influencing the limiting physico-chemical characteristics of the two polyphenols. Besides, they showed to be biocompatible and to protect the ocular surface epithelial cells from oxidative stress. In summary, the two systems may be considered as good candidates for the subsequent stage of drug development. Regarding liposomes and contact lenses loaded with micelles, further adjustment in the design and performance of the assays has to be carried out, in order to fully exploit their possibilities.