Improved anti-tumor efficiency against prostate cancer by docetaxel-loaded PEG-PCL micelles.
This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.
State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Ming-Ji
MJ
Jin
State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.|Yanbian University Hospital, Yanji, 133000, China.
Sheng-Jun
SJ
Piao
Yanbian University Hospital, Yanji, 133000, China.
Tie-Xiong
TX
Jin
Yanbian University Hospital, Yanji, 133000, China.
Zhe-Hu
ZH
Jin
Yanbian University Hospital, Yanji, 133000, China.
Xue-Zhe
XZ
Yin
State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. zggao@imm.ac.cn.|Yanbian University Hospital, Yanji, 133000, China. zggao@imm.ac.cn.
Zhong-Gao
ZG
Gao
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D008823:Micelles; D011091:Polyesters; D043823:Taxoids; D000077143:Docetaxel; C016240:polycaprolactone; D011092:Polyethylene Glycols