Synthesis, characterization and drug loading property of Monomethoxy-Poly(ethylene glycol)-Poly(ε-caprolactone)-Poly(D,L-lactide) (MPEG-PCLA) copolymers.
Amphiphilic block copolymers have attracted a great deal of attention in drug delivery systems. In this work, a series of monomethoxy-poly (ethylene glycol)-poly (ε-caprolactone-co-D,L-lactide) (MPEG-PCLA) copolymers with variable composition of poly (ε-caprolactone) (PCL) and poly (D,L-lactide) (PDLLA) were prepared via ring-opening copolymerization of ε-CL and D,L-LA in the presence of MPEG and stannous octoate. The structure and molecular weight were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The crystallinity, hydrophilicity, thermal stability and hydrolytic degradation behavior were investigated in detail, respectively. The results showed that the prepared amphiphilic MPEG-PCLA copolymers have adjustable properties by altering the composition of PCLA, which make it convenient for clinical applications. Besides, the drug loading properties were also studied. Docetaxel (DTX) could be entrapped in MPEG-PCLA micelles with high loading capacity and encapsulation efficiency. And all lyophilized DTX-loaded MPEG-PCLA micelles except MPEG-PCL micelles were readily re-dissolved in normal saline at 25 °C. In addition, DTX-loaded MPEG-PCLA micelles showed a slightly enhanced antitumor activity compared with free DTX. Furthermore, DTX micelles exhibited a slower and sustained release behavior in vitro, and higher DTX concentration and longer retention time in vivo. The results suggested that the MPEG-PCLA copolymer with the adjustable ratio of PCL to PDLLA may be a promising drug delivery carrier for DTX.
Department of Orthopaedic Surgery, Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, 325027, PR China.|R&D Center of New Product, Guangdong Zhongsheng Pharmaceutical Co., Ltd., Dongguan, 523325, PR China.|State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, PR China.
BingYang
B
Chu
R&D Center of New Product, Guangdong Zhongsheng Pharmaceutical Co., Ltd., Dongguan, 523325, PR China.
Lan
L
Zhang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, PR China.
Ying
Y
Qu
R&D Center of New Product, Guangdong Zhongsheng Pharmaceutical Co., Ltd., Dongguan, 523325, PR China.
XiaoXin
X
Chen
Department of Orthopaedic Surgery, Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, 325027, PR China.
JinRong
J
Peng
Department of Orthopaedic Surgery, Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, 325027, PR China.
YiXing
Y
Huang
R&D Center of New Product, Guangdong Zhongsheng Pharmaceutical Co., Ltd., Dongguan, 523325, PR China.
ZhiYong
Z
Qian
J Control Release. 2011 Oct 30;155(2):262-71
21704664
J Biomed Nanotechnol. 2013 Feb;9(2):147-57
23627041
Nat Nanotechnol. 2007 Dec;2(12):751-60
18654426
Int J Pharm. 2016 Mar 16;500(1-2):345-59
26794876
Biomaterials. 2003 Dec;24(27):4977-85
14559011
Clin Cancer Res. 2004 Jun 1;10(11):3708-16
15173077
Curr Drug Metab. 2012 May 1;13(4):338-53
22443531
J Control Release. 2001 Jun 15;73(2-3):137-72
11516494
Biomaterials. 2013 Jan;34(4):1413-32
23164423
Int J Pharm. 2015;486(1-2):356-66
25840274
Chem Mater. 2012 Mar 13;24(5):840-853
22707853
J Control Release. 2005 Dec 5;109(1-3):169-88
16289422
Int J Pharm. 2013 Jun 25;450(1-2):331-7
23587966
J Mater Sci Mater Med. 2000 Apr;11(4):227-33
15348037
Ann Oncol. 2007 Dec;18(12):2009-14
17785767
Acc Chem Res. 2014 Aug 19;47(8):2390-6
24852135
Ann Oncol. 2010 Feb;21(2):382-8
19633055
J Control Release. 2010 Dec 1;148(2):255-63
20816710
Chem Soc Rev. 2011 Mar;40(3):1761-76
21082079
J Mech Behav Biomed Mater. 2012 Aug;12:29-38
22659093
Biomaterials. 2004 May;25(11):1975-81
14741611
J Control Release. 2007 Oct 8;122(3):365-74
17574288
Nat Rev Drug Discov. 2010 Aug;9(8):615-27
20616808
Int J Pharm. 2015 Nov 10;495(1):265-75
26325322
J Mech Behav Biomed Mater. 2012 May;9:100-12
22498288
Int J Pharm. 2011 Jul 29;414(1-2):251-9
21596124