Octreotide-modified and pH-triggering polymeric micelles loaded with doxorubicin for tumor targeting delivery

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• 作者：Jiangxiu  ; Niu^a ;   ; ^b ; Zhigui  ; Su^a ; Yanyu  ; Xiao^a ; Aiwen  ; Huang^a ;   ; ^c ; Hongying  ; Li^a ; Xiao  ; Bao^a ; Sai  ; Li^a ; Yinan  ; Chen^a ; Mingjie  ; Sun^a ; Qineng  ; Ping^a ;   ; ^{pingqn2004@yahoo.cn} ;   ; ^{pingqn@cpu.edu.cn}
• 关键词：Targeting delivery ; Micelles ; Long circulation ; pH sensitivity ; Octreotide-mediated endocytosis
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2012
• 出版时间：23 January 2012
• 年：2012
• 卷：45
• 期：1-2
• 页码：216-226
• 全文大小：1410 K

文摘

A multifunctional mixed micelle was assembled for drug targeting delivery by combining two newly synthesized amphiphilic polymers, which were octreotide-polyethylene glycol-monostearate (OPMS) and N-octyl-N-succinyl-O-carboxymethyl chitosan (OSCC), respectively. The mixed micelle was designed to be characterized with long circulation, somatostatin receptors (SSTR)-mediated endocytosis and pH sensitivity. A series of assembling proportions of OPMS and OSCC was tested to reveal the effect of compositions on the functions. The particle size, zeta potential, drug loading and critical micelle concentration were examined. The dialysis test indicated a pH-triggering release behavior of the doxorubicin-loaded mixed micelle (DLMM), and faster release in acidic media (pH 4.0?.0) in response to the protonation of carboxyl group. In addition, the PEG segments could efficiently protect the mixed micelle from plasma protein adsorption in vitro, and the DLMM composed of 20 % OPMS and 80 % OSCC provided the longest residence time after intravenous injection in rats in vivo. Due to SSTR mediated endocytosis, the significantly higher uptake of DLMM was observed in the tumor cells (SMMC-7721), compared with that in the normal cells (CHO) without SSTR expression. All the results suggested that the mixed micelle with multifunctional characteristics could be used as an effective approach for tumor treatment.