Journal
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volume 49, Issue -, Pages 348-355Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.msec.2015.01.033
Keywords
Nanoparticles; Multidrug resistance; Poloxamer 235; PLGA-TPGS; Breast cancer
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Funding
- Beijing Top Level Health Scientific Innovation Personnel Training Plan [2013-3-047]
- Open Research Fund Program of the State Key Laboratory of Virology of China [2014KF004]
- National High Technology Research and Development Program (863 Program) [2011AA02A111]
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Multidrug resistance (MDR) is a major hurdle to the success of cancer chemotherapy. Poloxamers have been shown to reverse MDR by inhibiting the P-glycoprotein (P-gp) pump. The objective of this research is to test the feasibility of docetaxel-loaded PLGA-TPGS/Poloxamer 235 nanoparticles to overcome MDR in docetaxel-resistant human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by a modified nanoprecipitation method using PLGA-TPGS and PLGA-TPGS/Poloxamer 235 mixture, respectively. The PLGA-TPGS/Poloxamer 235 nanoparticles were of spherical shape and have a rough and porous surface. The docetaxel-loaded PLGA-TPGS/Poloxamer 235 porous nanoparticles which had an average size of around 180 nm with a narrow size distribution were stable, showing almost no change in particle size and surface charge during the 3-month storage period. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PLGA-TPGS/Poloxamer 235 porous nanopartides (PPNPs) in docetaxel-resistant human breast cancer cell line, MCF-7/TXT, in comparison with PLGA-TPGS nanoparticles (PTNPs). The PLGA-TPGS/Poloxamer 235 porous nanoparticles produced significantly higher level of toxicity than both of PLGA-TPGS nanoparticle formulation and Taxotere (R) both in vitro and in vivo, indicating docetaxel-loaded PLGA-TPGS/Poloxamer 235 porous nanoparticles have significant potential for the treatment of breast cancer. (C) 2015 Elsevier B.V. All rights reserved.
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