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Shikha P Barman, Yang Li, Laura Kaminski, Kevin Ward; Sustained Release of Small, Hydrophilic Peptides to the Ocular Surface via NanoM™. Invest. Ophthalmol. Vis. Sci. 2018;59(9):238.
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There is increasing interest in the use of therapeutic ophthalmic peptides to develop therapies in dry eye, microbial keratitis, corneal injury, etc. This is due to the high receptor specificity of peptides, promising more effective therapy compared to small molecule pharmaceutics. Included are cell-penetrating peptides (CPP), which can act as transporters for therapeutic peptides. Although the peptides 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 have hypothesized that it is feasible to achieve sustained release of a hydrophilic small molecule peptide via a novel ocular insert NanoM™. The NanoM™ is a biodegradable ocular insert that is self-administered into the conjunctival fornix and which releases sustained levels of peptide over the required duration. In contrast, eye-drops of peptides are administered ~ 5 times daily to achieve the desired effect. Additionally, we hypothesized that peptide-containing matrices can provide protection from proteolysis, while providing a consistent supply of the intact therapeutic. For the peptide, we have selected a 39-mer poly (amino acid), with high solubility in water. The peptide was selected due to its similarity in sequence to several therapeutic peptides under clinical testing. We present data that focus on design characteristics of the matrices.
Design parameters included polymeric compositions as they affect in-vitro release of the peptide, 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.
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 peptide-containing inserts contained 2-5% drug, <5% burst and near-linear release profiles to multiple days.
The data demonstrate that water-soluble peptides can be released in a sustained manner via NanoM™.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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