期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 92, 期 -, 页码 183-193出版社
ELSEVIER
DOI: 10.1016/j.ejps.2016.07.007
关键词
Gemcitabine; Nanoparticle; Long-circulation; Pharmacokinetics; Anti-cancer
资金
- Science & Engineering Research Board (SERB), Department of Science and Technology (DST), New Delhi, India [SR/FT/LS-107/2012]
- INSPIRE Fellowship
The anticancer potential of gemcitabine, a nucleoside analog, is compromised due to the enzymatic degradation into inactive form leading to the short half-life in systemic circulation. Novel delivery strategies are required to improve therapeutic efficacy of this potential drug. Monomethoxy polyethylene glycol amine-polylactide-co-glycolide (mPEG-PLGA) co-polymer was synthesized and characterized by FTIR and H-1 NMR. Gemcitabine loaded mPEG-PLGA nanoparticles (NPs) were developed and investigated for pharmacokinetic profile and in vivo anticancer activity. The mPEG-PLGA NPs (size: 267 +/- 10 nm, zeta potential: -17.5 +/- 0.2 mV) exhibited sustained drug release profile and were found to be compatible with blood. The mPEG-PLGA NPs were able to evade the uptake by macrophages (i.e. THP-1 and J774A) by reducing the adsorption of proteins on the surface of NPs. The enhanced cellular uptake and cell cytotoxicity was observed by mPEG-PLGA NPs in MiaPaCa-2 and MCF-7 cells. The half-life of gemcitabine in mPEG-PLGA NPs was remarkably enhanced (19 folds) than native gemcitabine. Further, the pharmacokinetic modulation of gemcitabine using mPEG-PLGA-NPs was translated in improved anticancer efficacy as compared to native gemcitabine in Ehrlich ascites bearing Balb-c mice. The results demonstrated the potential of long-circulatory nanoparticles in improving the pharmacokinetic profile and in-turn the anticancer efficacy of gemcitabine. (C) 2016 Published by Elsevier B.V.
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