High tolerated paclitaxel nano-formulation delivered by poly (lactic-co-glycolic acid)-g-dextran micelles to efficient cancer therapy.
The amphiphilic graft copolymer poly (lactic-co-glycolic acid)-g-dextran (Dex-PLGA) was successfully synthesized to fabricate micelles for the delivery of paclitaxel with low critical micelle concentration (CMC). The sizes of paclitaxel-loaded Dex-PLGA (Dex-PLGA/PTX) micelles were kept below 100nm with a relatively narrow size distribution. This novel PTX nano-formulation was found to exhibit slightly stronger in vitro cytotoxicity against SKOV-3, OVCAR-8 and MCF-7 cells with Taxol®. However, it could overcome the drug resistance of multi-drug resistant human breast carcinoma cells (MCF-7/Adr cells). The maximum tolerated dose (MTD) of Dex-PLGA/PTX after a single dose was more than 200mg PTX/kg, which were 8-fold higher than that of Paclitaxel Injection. The in vivo antitumor activity results indicated that Dex-PLGA/PTX micelles treatments effectively suppressed the tumor growth and highly reduced the toxicity against animals than Taxol® and could eliminate the SKOV-3 tumor by highly increasing the drug dose.


BACKGROUND
Chemotherapy for cancer has always been hampered the toxic side effect of the drugs. Nanotechnology has helped to produce various drug delivery systems to minimize these side effects. In this article, the authors designed dextran-based micelles loaded with paclitaxel. They showed effective anti-tumor activity in both in vitro and in vivo experiments with significant lower systemic toxicity.
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China; Puai Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Ping
P
Liu
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
Jun-Qing
JQ
Situ
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
Wei-Shuo
WS
Li
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
Chun-Lei
CL
Shan
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
Jian
J
You
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
Hong
H
Yuan
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
Fu-Qiang
FQ
Hu
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China. Electronic address: duyongzhong@zju.edu.cn.
Yong-Zhong
YZ
Du
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003911:Dextrans / Q000737:chemistry / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D051379:Mice; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D003911:Dextrans; D008823:Micelles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel
Dextran; Drug delivery; Maximum tolerated dose (MTD); Paclitaxel; Tumor therapy