期刊
JOURNAL OF CONTROLLED RELEASE
卷 165, 期 1, 页码 82-89出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2012.10.010
关键词
Contact lenses; Nanoparticles; Silicone gel; Timolol; Ophthalmic drug delivery; Beagle dogs
资金
- Glaucoma Foundation
- National Science Foundation [1129932]
- Directorate For Engineering
- Div Of Civil, Mechanical, & Manufact Inn [1129932] Funding Source: National Science Foundation
Glaucoma is the second major cause of blindness in the world after cataract. Glaucoma management through eye drops that reduce the intraocular pressure (IOP) has major deficiencies including low patient compliance and low bioavailability. Extended wear contact lenses that deliver glaucoma drugs for extended periods could increase patient compliance, while also increasing the bioavailability. To develop extended wear contact lenses that can also provide extended glaucoma therapy, we disperse nanoparticles of PGT (propoxylated glyceryl triacylate) that contain a glaucoma drug timolol. The particles can also be loaded into prefabricated lenses by soaking the lenses in a solution of particles in ethanol. The particle loaded gels can release timolol in phosphate buffered saline (PBS) for about a month at room temperature. The most likely rate controlling mechanism is hydrolysis of the ester bond that links timolol to the PGT matrix, but other mechanisms such as water and drug diffusion, drug dissolution, drug-polymer chain cleavage, time-dependent drug permeability within the polymeric matrix, etc. may also be important. Nanoparticle incorporation in the silicone hydrogels results in reduction in ion and oxygen permeabilities, and an increase in modulus, and the impact on each of these properties is proportional to the particle loading. A gel with 5% particle loading can deliver timolol at therapeutic doses for about a month at room temperature, with a minimal impact on critical lens properties. Preliminary animal studies in Beagle dogs conducted with lenses in which particles are loaded by soaking the lenses in ethanol show a reduction in IOP. (C) 2012 Elsevier B.V. All rights reserved.
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