期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 9, 期 1, 页码 130-140出版社
ELSEVIER
DOI: 10.1016/j.nano.2012.03.004
关键词
Minocycline; Diabetic retinopathy; Liposomes; Transcriptomics; Inflammation
资金
- Juvenile Diabetes Research Foundation (JDRF) Diabetic Retinopathy Center [4-2002-455]
- JDRF postdoctoral fellowship
- Pennsylvania Tobacco Settlement Funds
- American Diabetes Association
- National Eye Institute [L01 EY021716, R01 EY18336-02, EY020582]
Nanoliposomal technology is a promising drug delivery system that could be employed to improve the pharmacokinetic properties of clearance and distribution in ocular drug delivery to the retina. We developed a nanoscale version of an anionic, cholesterol-fusing liposome that can encapsulate therapeutic levels of minocycline capable of drug delivery. We demonstrate that size extrusion followed by size-exclusion chromatography can form a stable 80-nm liposome that encapsulates minocycline at a concentration of 450 +/- 30 mu M, which is 2% to 3% of loading material. More importantly, these nontoxic nanoliposomes can then deliver 40% of encapsulated minocycline to the retina after a subconjunctival injection in the STZ model of diabetes. Efficacy of therapeutic drug delivery was assessed via transcriptomic and proteomic biomarker panels. For both the free minocycline and encapsulated minocycline treatments, proinflammatory markers of diabetes were downregulated at both the messenger RNA and protein levels, validating the utility of biomarker panels for the assessment of ocular drug delivery vehicles.
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