Su Chia-Wei, Chiang Min-Yu, Lin Yu-Ling, Tsai Nu-Man, Chen Yen-Po, Li Wei-Ming, Hsu Chin-Hao, Chen San-Yuan
J Biomed Nanotechnol. 2016 May;12(5):962-72. doi: 10.1166/jbn.2016.2227.
For oral anti-cancer drug delivery, a new chitosan-lipid nanoparticle with sodium dodecyl sulfate modification was designed and synthesized using a double emulsification. TEM examination showed that the DOX-loaded nanoparticles, termed D-PL/TG NPs, exhibited a unique core-shell configuration composed of multiple amphiphilic chitosan-lecithin reverse micelles as the core and a triglyceride shell as a physical barrier to improve the encapsulation efficiency and reduce the drug leakage. In addition, the D-PL/TG NPs with sodium dodecyl sulfate modification on the surface have enhanced stability in the GI tract and increased oral bioavailability of doxorubicin. In vitro transport studies performed on Caco-2 monolayers indicated that the D-PL/TG NPs enhanced the permeability of DOX in the Caco-2 monolayers by altering the transport pathway from passive diffusion to transcytosis. The in vivo intestinal absorption assay suggested that the D-PL/TG NPs were preferentially absorbed through the specialized membranous epithelial cells (M cells) of the Peyer's patches, resulting in a significant improvement (8-fold) in oral bioavailability compared to that of free DOX. The experimental outcomes in this work demonstrate that the D-PL/TG NPs provide an exciting opportunity for advances in the oral administration of drugs with poor bioavailability that are usually used in treating tough and chronic diseases.
对于口服抗癌药物递送,采用双乳化法设计并合成了一种经十二烷基硫酸钠修饰的新型壳聚糖-脂质纳米颗粒。透射电子显微镜检查显示,负载阿霉素的纳米颗粒(称为D-PL/TG NPs)呈现出独特的核壳结构,其核心由多个两亲性壳聚糖-卵磷脂反胶束组成,外壳为甘油三酯,作为物理屏障以提高包封效率并减少药物泄漏。此外,表面经十二烷基硫酸钠修饰的D-PL/TG NPs在胃肠道中具有更高的稳定性,并提高了阿霉素的口服生物利用度。在Caco-2单层细胞上进行的体外转运研究表明,D-PL/TG NPs通过将转运途径从被动扩散改变为转胞吞作用,增强了阿霉素在Caco-2单层细胞中的渗透性。体内肠道吸收试验表明,D-PL/TG NPs优先通过派尔集合淋巴结的特化膜性上皮细胞(M细胞)吸收,与游离阿霉素相比,口服生物利用度显著提高(8倍)。这项工作中的实验结果表明,D-PL/TG NPs为通常用于治疗疑难和慢性疾病的生物利用度差的药物口服给药的进展提供了一个令人兴奋的机会。