Effect of surface ligand density on cytotoxicity and pharmacokinetic profile of docetaxel loaded liposomes

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• 作者：Chun Chu ; Ping Xu ; Haoyue Zhao ; Qing Chen ; Dawei Chen ; Haiyang Hu ; Xiuli Zhao ; Mingxi Qiao ; ^{qiaomingxi@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Docetaxel ; Liposomes ; Biotin ; Ligand density ; Tumor targeting
• 刊名：Asian Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：11
• 期：5
• 页码：655-661
• 全文大小：1314 K

文摘

Various biotin-modified liposomes incorporated with docetaxel (DTX) were prepared to study the effect of surface biotin density on the pharmacokinetic profile of the liposome. Four types of liposomes such as PEG modified liposome (PDL), 0.5% (mol) biotin modified liposome (0.5BDL), 1% (mol) biotin modified liposome (1BDL) and 2% (mol) biotin modified liposome (2BDL) were prepared using thin film dispersion method. The prepared liposomes were characterized by measuring encapsulation efficiency (EE), particle size, Zeta-potential, physical stability and drug release profiles in vitro. MTT assay was performed to elevate the cytotoxicity of liposomes on MCF-7 cells. In vivo evaluation was further performed to investigate the effect of biotin surface density on the pharmacokinetic profiles. All the prepared liposomes exhibited high encapsulation efficiency, small particle size, narrow particle distribution and sustained release profiles in vitro. In MTT assay, 0.5BDL showed largest tumor cell toxicity, compared with DTX solution. All liposomes containing DTX showed prolonged blood circulation in vivo, and 0.5BDL showed the longest circulation time among the biotin modified liposome. Surface modification of liposome had a negative impact on the circulation of liposomes in the blood, which needs to be considered when designing the ligand mediated targeting delivery systems. A proper amount of biotin liposome with 0.5% molar ratio is expected to produce the best anti-tumor effect.