Zaki Noha M
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University , Cairo , Egypt and.
Drug Deliv. 2014 Jun;21(4):265-75. doi: 10.3109/10717544.2013.838808. Epub 2013 Oct 4.
The aim of this was to investigate and compare the chemosensitizing effect of some pharmaceutical excipients (TPGS, Pluronic P85 and chitosan) by evaluating the cytotoxicity of the chemotherapeutic drug Hydroxy Camptothecin (HCPT) loaded into PLGA nanoparticles. Different nanoparticles formulations were developed and evaluated for size, zeta potential, morphology, loading and encapsulation efficiency as well as in vitro drug release. The cytotoxicity of the nanoparticles was evaluated by MTT assay in A549 (human lung carcinoma cell line) and HT29 (human colon carcinoma cell line) whereas their cellular uptake was determined by confocal laser scanning microscopy and microfluorimetry assay. The results revealed that nanoparticles possessed a desirable nanometric size (revealed by dynamic light scattering measurements and TEM) with appreciable HCPT encapsulation (>48%) and negative surface charge that was switched to positive upon coating with chitosan. The nanoparticles adopted a sustained release phase preceded by initial burst of HCPT that was reduced by chitosan coating. The cytotoxicity of the nanoparticles in A549 and HT29 cells was significantly augmented compared to simple drug solution and basic nanoparticles without excipients. The excipients could be ranked according to their IC50 lowering effect in the following order [TPGS (sixfold lower IC50) > Pluronic P85 > Chitosan]. The augmented cytotoxicity and chemosensitizing effect might be attributed to overcoming drug efflux (in case of TPGS 1000 or Pluronic P85) and/or maximizing internalization by cancer cells (chitosan coating). Acting as chemopotentiators, the studied excipients could have potential in reducing therapeutic HCPT doses and minimizing adverse effects in lung and colon chemotherapy.
本研究旨在通过评估负载化疗药物羟基喜树碱（HCPT）的聚乳酸-羟基乙酸共聚物（PLGA）纳米粒的细胞毒性，来研究和比较某些药用辅料（维生素E聚乙二醇琥珀酸酯、普朗尼克P85和壳聚糖）的化学增敏作用。制备了不同的纳米粒制剂，并对其粒径、zeta电位、形态、载药量、包封率以及体外药物释放进行了评估。通过MTT法在A549（人肺癌细胞系）和HT29（人结肠癌细胞系）中评估纳米粒的细胞毒性，而通过共聚焦激光扫描显微镜和微荧光测定法确定其细胞摄取情况。结果显示，纳米粒具有理想的纳米尺寸（通过动态光散射测量和透射电子显微镜显示），HCPT包封率可观（>48%），表面带负电荷，用壳聚糖包被后变为正电荷。纳米粒呈现出持续释放阶段，在此之前有HCPT的初始突释，壳聚糖包被可减少初始突释。与简单药物溶液和不含辅料的基础纳米粒相比，纳米粒在A549和HT29细胞中的细胞毒性显著增强。辅料可根据其降低IC50的效果按以下顺序排列[维生素E聚乙二醇琥珀酸酯（IC50降低六倍）>普朗尼克P85>壳聚糖]。增强的细胞毒性和化学增敏作用可能归因于克服药物外排（在维生素E聚乙二醇琥珀酸酯1000或普朗尼克P85的情况下）和/或使癌细胞的内化最大化（壳聚糖包被）。作为化学增效剂，所研究的辅料在降低治疗性HCPT剂量以及使肺癌和结肠癌化疗中的不良反应最小化方面可能具有潜力。
