Nano Drug Delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Int J Pharm. 2012 Nov 1;437(1-2):172-7. doi: 10.1016/j.ijpharm.2012.08.008. Epub 2012 Aug 14.
Gemcitabine is a known cytotoxic agent with a wide spectrum of antitumor activity. It has been employed in therapeutic regimens for various malignancies such as the lung, ovary, breast, and bladder cancers. It also has been used in the treatment of pancreatic cancer, in combination chemotherapy of non-small cell lung cancer (NSCLC) and in leukemia. Its effect results from incorporation into DNA with subsequent inhibition of cell proliferation. Unfortunately, Gemcitabine is rapidly metabolized by the so-called cytidine-deaminase which limits its efficacy. Because of extensive deamination by intestinal cells, its oral administration results in very low bioavailability. The aim of this study was to introduce an oral formulation of the drug for the first time and improve its physicochemical properties. Chitosan nanoparticles containing were produced based on ionic gelation method and tripolyphosphate (TPP). Physicochemical properties such as particle size and shape, loading efficiency and release rate were evaluated. Oral absorption of both free and nanoparticle-loaded drugs was measured using the rat intestinal sac model. The Gemcitabine-loaded chitosan nanoparticles were spherical with a mean size of 95±8 nm and high drug loading (63%). The nanoparticles showed controlled release pattern characterized by a fast initial release (61%) during the first 8h, followed by slower and continuous release (74.66%). The absorption study showed that Gemcitabine intestinal transport increased 3-5 folds by loading in chitosan nanocarrier.
盐酸吉西他滨是一种具有广谱抗肿瘤活性的已知细胞毒性药物。它已被用于治疗各种恶性肿瘤，如肺癌、卵巢癌、乳腺癌和膀胱癌。它还被用于治疗胰腺癌、非小细胞肺癌（NSCLC）联合化疗和白血病。其作用是通过掺入 DNA 来抑制细胞增殖。不幸的是，盐酸吉西他滨被所谓的胞嘧啶脱氨酶迅速代谢，这限制了它的疗效。由于肠道细胞的广泛脱氨作用，其口服给药导致生物利用度非常低。本研究的目的是首次介绍该药物的口服制剂，并改善其物理化学性质。基于离子凝胶法和三聚磷酸钠（TPP）制备了载盐酸吉西他滨的壳聚糖纳米粒。评估了粒径和形状、载药效率和释放率等物理化学性质。采用大鼠肠囊模型测定游离药物和载药纳米粒的口服吸收。盐酸吉西他滨载壳聚糖纳米粒呈球形，平均粒径为 95±8nm，载药率高（63%）。纳米粒呈现出快速初始释放（61%）的控制释放模式，在最初 8 小时内，随后是较慢和持续的释放（74.66%）。吸收研究表明，盐酸吉西他滨经壳聚糖纳米载体包载后，肠道转运增加了 3-5 倍。
