Xu Hang, Zhang Lu, Li Lin, Liu Yang, Chao Yanhui, Liu Xiaolin, Jin Zeng, Chen Yinrong, Tang Xing, He Haibing, Kan Qiming, Cai Cuifang
Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wen Hua Road, Shenyang, China.
University of Alberta, 116 St. and 85 Ave, Edmonton, Alberta, Canada.
AAPS PharmSciTech. 2017 Aug;18(6):2120-2130. doi: 10.1208/s12249-016-0693-x. Epub 2016 Dec 27.
In order to achieve high drug loading and high entrapment efficiency, a doxorubicin-cholesteryl hemisuccinate ion-pair complex (DCHIP) was formed, and the ion-pair complex liposomes (DCHIP-Lip) were prepared based on conventional thin-film dispersion method. Firstly, DCHIP was fabricated and confirmed with FTIR, H-NMR, DSC, and XRD techniques. Afterwards, DCHIP-Lip were prepared and evaluated in terms of particle size, zeta potential, entrapment efficiency, and drug loading content. Finally, the in vitro and in vivo behavior of liposomes was further investigated. The DCHIP-Lip had a nanoscale particle size of about 120 nm with a negative zeta potential of about -22 mV. In addition, the entrapment efficiency and drug loading content of DOX reached 6.4 ± 0.05 and 99.29 ± 0.3%, respectively. Importantly, the release of DCHIP-Lip was pH sensitive and increased cell toxicity against MCF-7 cells was achieved. Upon dilution, the liposomes were fairly stable under physiological conditions. The in vivo pharmacokinetic study indicated that the AUC of DOX in DCHIP-Lip was 11.48-fold higher than that of DOX-HCl solution and the in vivo antitumor activity of DCHIP-Lip showed less body weight loss and a significant prohibition effect of tumor growth. Based on these findings, it can be seen that the ion-pairing technology combined with conventional liposome drug loading method could be used to achieve high drug loading and it could be valuable for the study of liposomal delivery system.
为了实现高载药量和高包封率，制备了阿霉素-胆固醇半琥珀酸酯离子对复合物（DCHIP），并基于传统的薄膜分散法制备了离子对复合物脂质体（DCHIP-Lip）。首先，通过傅里叶变换红外光谱（FTIR）、氢核磁共振（H-NMR）、差示扫描量热法（DSC）和X射线衍射（XRD）技术制备并确认了DCHIP。之后，制备了DCHIP-Lip，并对其粒径、zeta电位、包封率和载药量进行了评估。最后，进一步研究了脂质体的体外和体内行为。DCHIP-Lip的纳米级粒径约为120 nm，zeta电位约为-22 mV。此外，阿霉素的包封率和载药量分别达到6.4±0.05和99.29±0.3%。重要的是，DCHIP-Lip的释放具有pH敏感性，并且对MCF-7细胞的细胞毒性增加。稀释后，脂质体在生理条件下相当稳定。体内药代动力学研究表明，DCHIP-Lip中阿霉素的曲线下面积（AUC）比阿霉素盐酸溶液高11.48倍，DCHIP-Lip的体内抗肿瘤活性显示体重减轻较少，对肿瘤生长有显著的抑制作用。基于这些发现，可以看出离子对技术与传统脂质体载药方法相结合可用于实现高载药量，这对于脂质体递送系统的研究可能具有重要价值。
