Feng Chao, Li Jing, Mu Yuzhi, Kong Ming, Li Yang, Raja Mazhar Ali, Cheng Xiao Jie, Liu Ya, Chen Xi Guang
College of Marine Life Science, Ocean University of China, Qingdao, 266003, China.
College of Marine Life Science, Ocean University of China, Qingdao, 266003, China.
Int J Biol Macromol. 2017 Jan;94(Pt A):170-180. doi: 10.1016/j.ijbiomac.2016.10.012. Epub 2016 Oct 8.
The primary constraints for efficient oral delivery of anticancer drugs include the efflux pump function of the multidrug transporter P-glycoprotein (P-gp) for anticancer drugs and the barriers to drug absorption in gastrointestinal (GI) tract. To improve bypassing P-gp drug efflux pumps and oral bioavailability of doxorubicin hydrochloride (DOX), Multilayer micro-dispersing system (MMS) was constructed by co-immobilization of DOX loaded chitosan/carboxymethyl chitosan nanogels (DOX:CS/CMCS-NGs), along with quercetin (Qu) in the core of multilayer sodium alginate beads (DOX:NGs/Qu-M-ALG-Beads). The obtained DOX:NGs/Qu-M-ALG-Beads possessed layer-by-layer structure and porous core with many nanoscale particles. The swelling characteristic and drug release results indicated that DOX:NGs/Qu-M-ALG-Beads exhibited favorable gastric acid tolerance and targeting release of intact DOX:CS/CMCS-NGs and Qu in small intestine. After oral administration of DOX:NGs/Qu-M-ALG-Beads in rats, DOX was effectively delivered into systemic circulation due to P-gp inhibitory properties of Qu. The absolute bioavailability reached 55.75%, about 18.65 folds higher than oral DOX. Tissue distribution results showed that the liver exhibited the highest DOX level, followed by kidney, heart, lung, and spleen. These results implied that DOX:NGs/Qu-M-ALG-Beads had great potential to be applied as dual drug delivery for oral chemotherapy.
高效口服递送抗癌药物的主要限制因素包括多药转运蛋白P-糖蛋白（P-gp）对抗癌药物的外排泵功能以及胃肠道（GI）中的药物吸收屏障。为了改善多柔比星盐酸盐（DOX）对P-gp药物外排泵的绕过作用和口服生物利用度，通过将负载DOX的壳聚糖/羧甲基壳聚糖纳米凝胶（DOX:CS/CMCS-NGs）与槲皮素（Qu）共固定在多层海藻酸钠珠（DOX:NGs/Qu-M-ALG-Beads）的核心中，构建了多层微分散系统（MMS）。所获得的DOX:NGs/Qu-M-ALG-Beads具有层层结构和带有许多纳米级颗粒的多孔核心。溶胀特性和药物释放结果表明，DOX:NGs/Qu-M-ALG-Beads表现出良好的耐胃酸性能，并且能在小肠中靶向释放完整的DOX:CS/CMCS-NGs和Qu。在大鼠口服DOX:NGs/Qu-M-ALG-Beads后，由于Qu对P-gp的抑制特性，DOX有效地递送至体循环。绝对生物利用度达到55.75%，比口服DOX高约18.65倍。组织分布结果表明，肝脏中的DOX水平最高，其次是肾脏、心脏、肺和脾脏。这些结果表明，DOX:NGs/Qu-M-ALG-Beads作为口服化疗的双药递送载体具有巨大的应用潜力。
