Co-Delivery of Timolol and Brimonidine with a Polymer Thin-Film Intraocular Device.

Autor:	Samy KE; 1 UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, California., Cao Y; 1 UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, California., Kim J; 1 UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, California., Konichi da Silva NR; 2 Department of Ophthalmology, University of California, San Francisco, San Francisco, California., Phone A; 2 Department of Ophthalmology, University of California, San Francisco, San Francisco, California., Bloomer MM; 2 Department of Ophthalmology, University of California, San Francisco, San Francisco, California., Bhisitkul RB; 2 Department of Ophthalmology, University of California, San Francisco, San Francisco, California., Desai TA; 3 Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California.
Jazyk:	angličtina
Zdroj:	Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics [J Ocul Pharmacol Ther] 2019 Mar; Vol. 35 (2), pp. 124-131. Date of Electronic Publication: 2019 Jan 07.
DOI:	10.1089/jop.2018.0096
Abstrakt:	Purpose: We developed a polycaprolactone (PCL) co-delivery implant that achieves zero-order release of 2 ocular hypotensive agents, timolol maleate and brimonidine tartrate. We also demonstrate intraocular pressure (IOP)-lowering effects of the implant for 3 months in vivo. Methods: Two PCL thin-film compartments were attached to form a V-shaped co-delivery device using film thicknesses of ∼40 and 20 μm for timolol and brimonidine compartments, respectively. In vitro release kinetics were measured in pH- and temperature-controlled fluid chambers. Empty or drug-loaded devices were implanted intracamerally in normotensive rabbits for up to 13 weeks with weekly measurements of IOP. For ocular concentrations, rabbits were euthanized at 4, 8, or 13 weeks, aqueous fluid was collected, and ocular tissues were dissected. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry. Results: In vitro studies show zero-order release kinetics for both timolol (1.75 μg/day) and brimonidine (0.48 μg/day) for up to 60 days. In rabbit eyes, the device achieved an average aqueous fluid concentration of 98.1 ± 68.3 ng/mL for timolol and 5.5 ± 3.6 ng/mL for brimonidine. Over 13 weeks, the drug-loaded co-delivery device resulted in a statistically significant cumulative reduction in IOP compared to untreated eyes (P < 0.05) and empty-device eyes (P < 0.05). Conclusions: The co-delivery device demonstrated a zero-order release profile in vitro for 2 hypotensive agents over 60 days. In vivo, the device led to significant cumulative IOP reduction of 3.4 ± 1.6 mmHg over 13 weeks. Acceptable ocular tolerance was seen, and systemic drug levels were unmeasurable.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu