Department of Pharmaceutical Technology, BIT campus, Anna University, Tiruchirappalli - 620 024, Tamilnadu, India.
Department of Pharmaceutics, SRM University, SRM Nagar, Kattankulathur - 603 203, Tamil Nadu, India.
Int J Biol Macromol. 2017 Nov;104(Pt B):1846-1852. doi: 10.1016/j.ijbiomac.2017.05.127. Epub 2017 May 22.
Clinical use of camptothecin (CPT) is hindered due to its poor water and oil solubility, active lactone ring instability and non-targeted toxicity. Recently we reported formulation of camptothecin microemulsions with increased solubility for the improved treatment of breast cancer. In this research chitosan stabilized camptothecin nanoemulsions (CHI-CPT-NEs) were formulated improve the cancer targeting efficiency of CPT. The developed NEs were characterized for their droplet size distribution, stability in plasma and evaluated for in-vitro drug release, in-vivo targeting potential, in-vitro hemolytic potential, cytotoxicity, genotoxicity and in-vivo biodistribution. The CHI-CPT-NEs showed uniform droplet size distribution, extended drug release (61.65±1.57% at 24h), tolerable hemolytic potential (16.4±1.4%), significant cytotoxicity (178±4.3ng/ml) against MCF-7 cancer cells and low DNA damage to lymphocytes. In-vivo biodistribution study conducted in 4T1-breast tumor xenograft BALB/c mice showed that 2495.22±174.66ng/gm of camptothecin was passively targeted to breast cancer by CHI-CPT-NEs compared to the non-stabilized nanoemulsion (1677.58±134.21ng/gm). Thus, passive targeting of developed CHI-CPT-NEs may provide a promising approach for the efficient breast cancer therapy.
喜树碱（CPT）的临床应用受到其水溶性和油溶性差、内酯环不稳定和非靶向毒性的限制。最近，我们报道了喜树碱微乳的配方，提高了溶解度，以改善乳腺癌的治疗效果。在这项研究中，我们制备了壳聚糖稳定的喜树碱纳米乳（CHI-CPT-NE），以提高 CPT 的癌症靶向效率。对所开发的 NE 进行了粒径分布、血浆稳定性的表征，并评估了其体外药物释放、体内靶向潜力、体外溶血潜能、细胞毒性、遗传毒性和体内生物分布。CHI-CPT-NE 表现出均匀的粒径分布、延长的药物释放（24 小时时为 61.65±1.57%）、可耐受的溶血潜能（16.4±1.4%）、对 MCF-7 癌细胞具有显著的细胞毒性（178±4.3ng/ml）和对淋巴细胞的低 DNA 损伤。在 4T1 乳腺癌异种移植 BALB/c 小鼠中的体内生物分布研究表明，与未稳定的纳米乳（1677.58±134.21ng/gm）相比，CHI-CPT-NE 被动靶向乳腺癌的喜树碱量为 2495.22±174.66ng/gm。因此，开发的 CHI-CPT-NE 的被动靶向可能为有效的乳腺癌治疗提供一种有前途的方法。
