Berko Y A, Funmilola A F, Akala E O
Center for Drug Research and Development, Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, 2300 4th Street, NW, Washington, DC 20059, USA.
Drug Research and Production Unit, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.
J Pharm Drug Deliv Res. 2021 Jan;10(1). Epub 2021 Jan 11.
The aim of this study is to design, fabricate and determine the cytotoxic effects of dual loaded paclitaxel and 17-AAG in stealth polymeric nanoparticles. The nanoparticles were fabricated by dispersion polymerization.
Two breast cancer cell lines (MCF-7 and SKBR-3) were cultured and treated with media only, blank nanoparticles, paclitaxel (as a free drug), 17-AAG (free drug), paclitaxel + 17-AAG combination (as free drugs), and paclitaxel + 17-AAG combination loaded in poly-ε-caprolactone stealth nanoparticles. Each drug in the combination was half the concentration of the single free drug.
The cytotoxic effects of the paclitaxel treatment and that of the combination (free drug) were found to be similar in both SKBR3 and MCF7 cell lines. Similar cytotoxic effects were observed for the drug combination both in the drug loaded nanoparticles formulation and in free drug form for both cell lines.
Both paclitaxel and 17-AAG were effectively loaded and released from the polymeric nanoparticles. Paclitaxel (free drug), paclitaxel-17AAG combination (free drug), and dual drug-loaded nanoparticles had similar cytotoxic effects on both cell lines. Paclitaxel and 17-AAG combination resulted in synergistic effect: paclitaxel in the combination with 17-AAG was half its original concentration and yielded similar cytotoxic effect. The dose of paclitaxel was reduced without lowering its therapeutic efficacy.
本研究旨在设计、制备并确定载有紫杉醇和17-AAG的隐形聚合物纳米粒的细胞毒性作用。纳米粒通过分散聚合法制备。
培养两种乳腺癌细胞系(MCF-7和SKBR-3),并用仅含培养基、空白纳米粒、紫杉醇(游离药物)、17-AAG(游离药物)、紫杉醇+17-AAG组合(游离药物)以及负载于聚ε-己内酯隐形纳米粒中的紫杉醇+17-AAG组合进行处理。组合中的每种药物浓度为单一游离药物浓度的一半。
在SKBR3和MCF7细胞系中,发现紫杉醇处理组与组合(游离药物)组的细胞毒性作用相似。对于两种细胞系,在载药纳米粒制剂和游离药物形式中均观察到药物组合具有相似的细胞毒性作用。
紫杉醇和17-AAG均能有效负载于聚合物纳米粒并从中释放。紫杉醇(游离药物)、紫杉醇-17AAG组合(游离药物)以及双载药纳米粒对两种细胞系均具有相似的细胞毒性作用。紫杉醇与17-AAG组合产生协同效应:组合中的紫杉醇浓度为其原始浓度的一半,但产生了相似的细胞毒性作用。在不降低治疗效果的情况下降低了紫杉醇的剂量。