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Shikha P Barman, Brendan Hackett, Kevin L Ward, Laura Kaminski; Sustained Release of Peptides to the Ocular Surface via NanoM™ Wafer. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4103.
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© ARVO (1962-2015); The Authors (2016-present)
Due to their high receptor specificity and biological activity, peptides can have higher potency than small molecule-based pharmaceutics. There is increasing interest in the use of peptides for therapy of dry eye, corneal abrasions, etc. However, due to rapid fluid clearance and naso-lacrimal losses, eye-drops lead to frequent dosing and eventual lack of patient compliance. Also, peptides are susceptible to proteolytic degradation, leading to short half-lives.A sustained release peptide-containing matrix can provide protection from proteolysis, while providing a consistent supply of the intact therapeutic to the eye. However, achieving gradual release of peptides, especially those with < 100 amino acids is a challenge, due to their water solubility and small molecular size.We are developing NanoM™ Wafer, an ocular insert that is self-administered into the conjunctival fornix and which releases a sustained concentration of peptide over a week. For the peptide, we have selected a 39-mer poly (amino acid), 3900 g/mole and with high solubility in water. We selected this model peptide due to its similarity in properties to several therapeutic peptides under research.We present an approach and data that focuses on design characteristics of the delivery system critical to its in-vivo performance.
Design parameters included compositions as they affect in-vitro release of the peptide, conditions for wafer fabrication that result in minimized oxidation of the peptide, and its protection from proteases.The matrices were fabricated using a proprietary process, with multifunctional attributes contributing to hydration into a hydrogel that form adhesive linkages to the eye. Peptide content (µg/mg), % degradants were analyzed by HPLC, morphology by SEM, % hydration by kinetics of water absorption and mucoadhesion on ocular tissue by a mechanical tester.
Systems had inter-connected nano-pores between 100-250 nm, thicknesses between 0.13-0.34 mm and drug encapsulation between 2-5%. Wafer compositions modulated mucoadhesivity, biodegradation and drug release. Each device contained 2-5% of intact drug, ~ 2% burst and 1.5-2.5 µg released/ day for 7 days The matrix hydrated in ~ 20 seconds. Mucoadhesion was rapid and adhered to ocular tissue for ~7 days.
The data demonstrate that water-soluble peptides of < 100 amino acids, can be released in a sustained manner via NanoM™, over 7 days.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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