期刊
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
卷 29, 期 2, 页码 216-228出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/jop.2012.0069
关键词
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资金
- National Eye Institute, National Institutes of Health [EY018426-02]
- National Institute of General Medical Sciences, National Institutes of Health [P20 GM104932]
- Health Resources and Services Administration (HRSA) [DIBT16663]
Purpose: The goal of this study was to develop and characterize indomethacin-loaded solid lipid nanoparticles (IN-SLNs; 0.1% w/v) for ocular delivery. Methods: Various lipids, homogenization pressures/cycles, Tween 80 fraction in the mixture of surfactants (Poloxamer 188 and Tween 80; total surfactant concentration at 1% w/v), and pH were investigated in the preparation of the IN-SLNs. Compritol (R) 888 ATO was selected as the lipid phase for the IN-SLNs, as indomethacin exhibited a highest distribution coefficient and solubility in this phase. Results: Homogenization at 15,000 psi for 6 cycles resulted in the smallest particle size. Increase in the Poloxamer 188 fraction resulted in decrease in the entrapment efficiency (EE). The mean particle size, polydispersity index, zeta-potential, and EE of the optimized formulation were 140 nm, 0.16, -21 mV, and 72.0%, respectively. IN-SLNs were physically stable post-sterilization and on storage for a period of 1 month (last timepoint tested). A dramatic increase in the chemical stability and in vitro corneal permeability of indomethacin was observed with the IN-SLN formulation in comparison to the indomethacin solution- (0.1% w/v) and indomethacin hydroxypropyl-beta-cyclodextrin-based formulations (0.1% w/v). Conclusion: Results from this study suggest that topical IN-SLNs could significantly improve ocular bioavailability of indomethacin.
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