Journal
BIOMATERIALS
Volume 35, Issue 7, Pages 2391-2400Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.11.086
Keywords
Biodegradable polymers; Cancer nanotechnology; Controlled release; Molecular biomaterial; Nanomedicine; Pharmaceutical nanotechnology
Funding
- National Natural Science Foundation of China [31270019, 51203085, 81272638]
- Program for New Century Excellent Talents in University [NCET-11-0275]
- Natural Science Foundation of Guangdong Province [S2012010010046, S2012040006820]
- China Postdoctoral Science Foundation [2012M520242]
- Science, Technology & Innovation Commission of Shenzhen Municipality [JCYJ20120616213729920, JCYJ20120614 191936420, KQC201105310021A, JC201005270308A]
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We report a strategy to make use of poly(lactic-co-glycolic acid) nanoparticle (PLGA NPs) for co-delivery of docetaxel (DTX) as a model anticancer drug together with vitamin E TPGS. The latter plays a dual role as a pore-forming agent in the nanopartides that may result in smaller particle size, higher drug encapsulation efficiency and faster drug release, and also as a bioactive agent that could inhibit P-glycoprotein to overcome multi-drug resistance of the cancer cells, The DTX-loaded PLGA NPs of 0, 10, 20 and 40% TPGS were prepared by the nanoprecipitation method and then characterized for their size and size distribution, surface morphology, physical status and encapsulation efficiency of the drug in the NPs. All four NPs were found of size ranged 100-120 nm and EE ranged 85-95% at drug loading level around 10%. The in vitro evaluation showed that the 48 h IC50 values of the free DTX and the DTX-loaded PLGA NPs of 0, 10,20% TPGS were 2.619 and 0.474, 0.040, 0.009 mu g/mL respectively, which means that the PLGA NPs formulation could be 5.57 fold effective than the free DTX and that the DTX-loaded PLGA NPs of 10 or 20% TPGS further be 11.85 and 52.7 fold effective than the DTX-loaded PLGA NPs of no TPGS (therefore, 66.0 and 284 fold effective than the free DTX). Xenograft tumor model and immunohistological staining analysis further confirmed the advantages of the strategy of co-delivery of anticancer drugs with TPGS by PLGA NPs. (c) 2013 Elsevier Ltd. All rights reserved.
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