期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 104, 期 1, 页码 165-177出版社
WILEY-BLACKWELL
DOI: 10.1002/jps.24234
关键词
lapatinib; paclitaxel; poorly water-soluble drugs; solubility; micelle; cancer chemotherapy; sensitize; human epidermal growth factor receptor-2; polymeric drug delivery systems; conjugation
资金
- National Key Basic Research Program of China (973 Program) [2013CB932502]
- Special Project for Nano-technology from Shanghai [12nm0501500]
- Shanghai Committee of Science and Technology, China [13NM1401504]
- National Science Foundation of China [81072175, 81372854, 81102010]
Lapatinib (LPT) could sensitize human epidermal growth factor receptor-2 (HER-2) positive breast cancer to paclitaxel (PTX) and induce synergetic action with PTX in preclinical test and phase II/III trial. In this study, LPT-conjugated poly (ethylene glycol) (PEG) and poly (lactic acid) (PLA) (LPT-PEG-PLA) was first synthesized and confirmed with H-1 Nuclear Magnetic Resonance and Matrix-Assisted Laser Desorption/ Ionization Time of Flight Mass Spectrometry, which was used for the preparation of a novel PEG-PLA combined micelles of LPT and PTX (PPM-LP). The obtained PPM-LP exhibited uniform, spherical shape with a size of 25.80 +/- 0.47 nm and zeta potential of -3.17 +/- 0.15 mv. PTX existed in molecular or amorphous forms in the micelles and superficial LPT could better delay PTX release. The cytotoxicity of PPM-LP with LPT conjugation against SKBr-3 cells (HER-2 positive) was found to be significantly increasing as compared with PPM-PTX, whereas there was no significant difference against MDA-MB-231 cells (HER-2 negative). PPM-LP could escape from endosomes and be distributed into cytoplasm and led to cell arrest in G2/M and G1/S phases simultaneously. Results of nucleus staining and flow cytometry confirmed that LPT could remarkably increase antineoplastic effect of PTX against SKBr-3 cells. All these results demonstrated that PPM-LP may be a promising drug delivery system for HER-2 positive breast cancer. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:165-177, 2015
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