Abstract
Purpose :
There is increasing interest in the use of therapeutic proteins for the development of therapies in dry eye, corneal injury, etc. This is due to the high receptor specificity of biologics, promising more effective therapy compared to small molecule pharmaceutics. Although these biological molecules vary in structure and properties, most of these have water solubility, potential to oxidize and susceptibility to proteolytic degradation. The synergistic result of these attributes imparts short half-lives and fleeting residence time on the ocular surface, compromising their therapeutic effect. We hypothesize that it is feasible to achieve sustained release of model proteins (IgG and BSA) of varying molecular weights via a novel ocular insert NanoM™. We have developed a platform nanostructured ocular insert (NanoM™) that is placed into the lower conjunctival fornix in a dry form. Rapid absorption of water results in a “hydrogel-like” delivery system, molding itself to the underlying tissue. This characteristic of the delivery system contributes to the biocompatibility and minimal immunogenicity at the target site. We present data that focus on design characteristics of the ocular delivery system.
Methods :
Design parameters included polymeric compositions as they affect in-vitro release of the protein, oxidation and its protection from proteases while encapsulated in NanoM. The matrices were fabricated multifunctional attributes resulting in a hydrogel that formed bioadhesive linkages to the ocular surface. Encapsulation (µg/mg) and degradants were analyzed by HPLC, morphology by SEM and mucoadhesion on bovine ocular tissue by a mechanical tester.
Results :
All drug-containing devices had pores between 100-250 nm, thicknesses between 0.13-0.200 mm with composition a key variable in mucoadhesivity, biodegradation and release of intact drug. The protein-containing inserts contained 2-5% drug, <5% burst and near-linear release profiles to multiple days. The pH range of the drug-delivery system as it biodegrades is 6.8-7.2, contributing to biocompatibility with underlying tissue as well as drug release.
Conclusions :
The data demonstrate that water-soluble proteins can be released in a sustained manner via NanoM™.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.