College of Marine Life Science, Ocean University of China, Qingdao 266003, PR China.
Int J Pharm. 2013 Nov 30;457(1):158-67. doi: 10.1016/j.ijpharm.2013.07.079. Epub 2013 Sep 9.
The present study investigated the ability of a polyelectrolyte complex (CS/CMCS-NPs), composed of chitosan (CS) and o-carboxymeymethy chitosan (CMCS) as a pH responsive carrier for oral delivery of doxorubicin hydrochloride (DOX). The obtained CS/CMCS-NPs were characterized for various parameters including morphology, particle size, zeta potential, entrapment efficiency and stability under the simulated GI tract conditions. The pH responsive stability of the DOX-loaded CS/CMCS nanoparticles (DOX:CS/CMCS-NPs) determined the drug release rate, which was lower in acidic pH than the neutral. Ex vivo intestinal adhesion and permeation indicated DOX:CS/CMCS-NGs were able to enhance absorption of DOX throughout the entire small intestine, especially in jejunum and ileum. Oral administration of DOX:CS/CMCS-NPs was effective to deliver DOX into blood, giving an absolute bioavailability of 42%. The tissue distribution and toxicity of DOX:CS/CMCS-NPs in rats showed low level of DOX in heart and kidney, and obviously decreased cardiac and renal toxicities. These results indicated CS/CMCS-NPs were highly efficient and safe as an oral delivery system for DOX.
本研究考察了由壳聚糖（CS）和羧甲基壳聚糖（CMCS）组成的聚电解质复合物（CS/CMCS-NPs）作为盐酸阿霉素（DOX）口服递送的 pH 响应载体的能力。所得到的 CS/CMCS-NPs 进行了各种参数的表征，包括形态、粒径、Zeta 电位、包封效率和在模拟胃肠道条件下的稳定性。载药 CS/CMCS 纳米粒（DOX：CS/CMCS-NPs）的 pH 响应稳定性决定了药物释放速率，在酸性 pH 下低于中性 pH。离体肠道黏附和渗透实验表明，DOX：CS/CMCS-NGs 能够增强 DOX 在整个小肠中的吸收，尤其是在空肠和回肠中。DOX：CS/CMCS-NPs 的口服给药能够有效地将 DOX 递送到血液中，绝对生物利用度为 42%。在大鼠中的组织分布和毒性研究表明，DOX：CS/CMCS-NPs 在心脏和肾脏中的 DOX 水平较低，并且明显降低了心脏和肾脏的毒性。这些结果表明，CS/CMCS-NPs 作为 DOX 的口服递送系统具有高效和安全的特点。
