Rongbin Huang, Lei Xiang, Ying Liu, Xiangping Deng, Xuan Cao, Lanfang Li, Cuiyun Yu, Yanming Chen, Guotao Tang
The First People's Hospital of Xiangtan City, Xiangtan, China.
Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics University of South China, Hengyang, China.
J Pharm Pharmacol. 2016 Jun;68(6):751-61. doi: 10.1111/jphp.12545. Epub 2016 Mar 28.
To develop an acid trigger release of antitumour drug delivery carriers, pH-sensitive amphiphilic poly (ethyleneglycol)-imine-benzoic-dipalmitate (PEG-I-dC16 ) polymers were designed and synthesized and the drug-loaded micelles were evaluated in vitro.
PEG-I-dC16 synthesized by Schiff base synthetic method and characterized by (1) H-NMR. To determine the drug-loading capacity, doxorubicin (DOX) was encapsulated in the micelles using membrane dialysis method. Zeta potential, particle size, drug-loading capacity, in vitro drug release in different pH conditions and cytotoxicity evaluation of micelles were carried out comparing with non-acid liable PEG-amide-benzoic-dipalmitate (PEG-A-dC16) polymers micelles. The cellular uptake and intracellular distribution of DOX were detected by flow cytometry and confocal laser scanning microscope.
Drug-loading capacity and encapsulation efficiency of micelle (PEG molecular weight 2k) were 12.7 ± 1.1% and 49.8 ± 2.2%, respectively. The average particle size was 72.3 ± 2.5 nm. The DOX release rate of PEG-I-dC16 micelles is much higher at pH 6.5 than at pH 7.4. DOX cellular uptake and nuclear accumulation of PEG-I-dC16 micelles were more efficiency than that of PEG-A-dC16 micelles.
The pH-sensitive PEG-I-dC16 micelles could be a promising drug delivery system for anticancer drugs.
为开发一种抗肿瘤药物递送载体的酸触发释放体系，设计并合成了对pH敏感的两亲性聚（乙二醇）-亚胺-苯甲酸-二棕榈酸酯（PEG-I-dC16）聚合物，并对载药胶束进行了体外评价。
通过席夫碱合成法合成PEG-I-dC16并用（1）H-NMR进行表征。为测定载药量，采用膜透析法将阿霉素（DOX）包封于胶束中。与非酸敏感的聚乙二醇-酰胺-苯甲酸-二棕榈酸酯（PEG-A-dC16）聚合物胶束相比，对胶束的zeta电位、粒径、载药量、不同pH条件下的体外药物释放以及细胞毒性进行了评价。通过流式细胞术和共聚焦激光扫描显微镜检测DOX的细胞摄取和细胞内分布。
胶束（PEG分子量2k）的载药量和包封率分别为12.7±1.1%和49.8±2.2%。平均粒径为72.3±2.5nm。PEG-I-dC16胶束在pH 6.5时的DOX释放速率远高于pH 7.4时。PEG-I-dC16胶束的DOX细胞摄取和核积累效率高于PEG-A-dC16胶束。
对pH敏感的PEG-I-dC16胶束可能是一种有前景的抗癌药物递送系统。
