期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 414, 期 1-2, 页码 251-259出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2011.05.014
关键词
Polymeric nanoparticle; Paclitaxel; Amphiphilic diblock copolymer; MPEG-PCL; Solid dispersion technique
资金
- National 863 project [2007AA021902, 2007AA021804]
- National Natural Science Foundation of China [NSFC20704027]
- Sichuan Key Project of Science and Technology [2007SGY019]
- Sichuan Prominent Young Talents Program [07ZQ026-033]
- Chinese Key Basic Research Program [2004CB518807]
Polymeric nanoparticles (NPs) have great potential application in achieving targeted delivery of anticancer drugs. Paclitaxel (PTX) loaded NPs were developed using biodegradable methoxy poly (ethylene glycol)-poly (epsilon-caprolactone) (MPEG-PCL) diblock copolymer by solid dispersion technique without toxic organic solvent. The lyophilized powder has been stored at room temperature for more than six months and still unchanged. PTX-loaded MPEG-PCL nanoparticles (PTX-NPs) displayed that the highest drug loading of PTX was about 25.6% and entrapment efficiency was over 98%, and the optimized average diameter and polydispersity index (PDI) were about 27.6 +/- 0.1 nm and 0.05, respectively. Moreover, experimental results shown PTX-NPs had sustained-release effects and its curve fitting followed the Higuchi model. The maximum tolerated dose (MTD) of PTX-NPs after single dose in Balb/c mice was above 80 mg PTX/kg body weight (b.w), which was 2.6-fold higher than that of Taxol (R) (30 mg PTX/kg b.w). The levels of PTX administrated PTX-NPs had obvious distinction to Taxol (R) in plasma, liver, spleen, kidneys, lungs, heart and tumor. Especially, the concentration of PTX in tumor administrated PTX-NPs was higher than administration of Taxol (R). All results suggested that we had contrived a simple, biodegradable, effective and controllable drug delivery system for paclitaxel. (C) 2011 Elsevier B.V. All rights reserved.
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