Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Int J Nanomedicine. 2011 Jan 12;6:119-28. doi: 10.2147/IJN.S15500.
The aim of this study was to prepare and evaluate mucoadhesive core-shell nanoparticles based on copolymerization of thiolated chitosan coated on poly methyl methacrylate cores as a carrier for oral delivery of docetaxel. Docetaxel-loaded nanoparticles with various concentrations were prepared via a radical emulsion polymerization method using cerium ammonium nitrate as an initiator. The physicochemical properties of the obtained nanoparticles were characterized by: dynamic light-scattering analysis for their mean size, size distribution, and zeta potential; scanning electron microscopy and transmission electron microscopy for surface morphology; and differential scanning calorimetry analysis for confirmation of molecular dispersity of docetaxel in the nanoparticles. Nanoparticles were spherical with mean diameter below 200 nm, polydispersity of below 0.15, and positive zeta potential values. The entrapment efficiency of the nanoparticles was approximately 90%. In vitro release studies showed a sustained release characteristic for 10 days after a burst release at the beginning. Ex vivo studies showed a significant increase in the transportation of docetaxel from intestinal membrane of rat when formulated as nanoparticles. Cellular uptake of nanoparticles was investigated using fluoresceinamine-loaded nanoparticles. Docetaxel nanoparticles showed a high cytotoxicity effect in the Caco-2 and MCF-7 cell lines after 72 hours. It can be concluded that by combining the advantages of both thiolated polymers and colloidal particles, these nanoparticles can be proposed as a drug carrier system for mucosal delivery of hydrophobic drugs.
本研究旨在制备和评价基于巯基化壳聚糖包覆在聚甲基丙烯酸甲酯核上的共聚体制备的作为多西紫杉醇口服给药载体的粘膜粘附核壳纳米粒子。通过使用硝酸铈铵作为引发剂的自由基乳液聚合方法制备了载有不同浓度多西紫杉醇的纳米粒子。通过动态光散射分析测定其平均粒径、粒径分布和zeta 电位；扫描电子显微镜和透射电子显微镜测定表面形态；差示扫描量热法分析确认多西紫杉醇在纳米粒子中的分子分散性来对所获得的纳米粒子的物理化学性质进行了表征。纳米粒子呈球形，平均直径低于 200nm，多分散性低于 0.15，zeta 电位值为正。纳米粒子的包封效率约为 90%。体外释放研究表明，在开始时的突释之后，具有持续释放 10 天的特征。体外研究表明，当将多西紫杉醇制成纳米粒子时，从大鼠肠膜中的转运显著增加。使用荧光素胺负载的纳米粒子研究了纳米粒子的细胞摄取。多西紫杉醇纳米粒子在 Caco-2 和 MCF-7 细胞系中 72 小时后显示出高细胞毒性作用。可以得出结论，通过结合巯基化聚合物和胶体粒子的优点，这些纳米粒子可以被提出作为用于粘膜传递疏水性药物的药物载体系统。
