期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 112, 期 -, 页码 474-482出版社
ELSEVIER
DOI: 10.1016/j.colsurfb.2013.07.039
关键词
Poly(ortho ester); Celecoxib; Nanoparticles; Solvent diffusion; Nile red; Cytotoxicity
资金
- NEI [P30EY013080]
- March of Dimes Grant [6-FY09-281]
- Fight For Sight Grant [FFS-PD-10-009]
- Knights Templar Eye Foundation, Flower Mound, TX
- Research to Prevent Blindness, New York, NY
The present investigation is aimed at improving the ocular bioavailability of a poorly water soluble drug, celecoxib, to offer new options in the treatment of chronic eye diseases, such as age-related macular degeneration and diabetic retinopathy. To do so, we developed a novel formulation of drug-loaded poly(ortho ester) nanoparticles (NPs). We characterized the NPs in terms of size, morphology, controlledrelease, degradation and cytocompatibity. Stable and transparent NP emulsions were prepared following a double emulsion solvent diffusion method employing poloxamer 188 as a stabilizer. Physical properties showed a narrow range size distribution of 151-164 nm with spherical morphology, negative zeta potentials and remarkably high celecoxib encapsulation efficiency (98%) and loading (64%) of poly(ortho ester) NPs. Drug release followed a zero-order release by a surface erosion-controlled mechanism without any burst effect. Degradation of poly(ortho ester) NPs was observed by measuring the concentration of initial degradation product such as, lactic acid. MU studies revealed minimal toxicity of NPs (up to 1 mg/ml) toward HER 293 cells. Poly(ortho ester) NPs were not internalized by either Muller or HEK 293 cells, which is highly desirable for a drug carrier to deliver the drugs for prolonged periods to the back of eye. These features have the potential to decrease the number of intraocular injections required to treat chronic eye diseases. (C) 2013 Elsevier B.V. All rights reserved.
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