a Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences , Isfahan University of Medical Sciences , Isfahan , Iran (the Islamic Republic of).
b Department of Medicinal Chemistry, School of Pharmacy , Isfahan University of Medical Sciences , Isfahan , Iran (the Islamic Republic of).
Pharm Dev Technol. 2018 Jan;23(1):41-54. doi: 10.1080/10837450.2017.1340950. Epub 2017 Jul 7.
To develop an effective therapeutic treatment, the potential of poly (lactic-co-glycolic acid)-polyethylene glycol-retinoic acid (PLGA-PEG-RA) polymeric micelles for targeted delivery of irinotecan to hepatocellular carcinoma (HepG2) and colorectal cancer cell lines (HT-29) was evaluated. PLGA-PEG-RA was synthesized by amide reaction of PLGA with NH2-PEG-NH and then PLGA-PEG-NH with RA and confirmed by FTIR and H NMR spectroscopy. Irinotecan-loaded nanomicelles were prepared using thin-film hydration method and the impact of various formulation variables on their particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), and mean release time (MRT) were assessed using a Taguchi design. TEM was used to observe morphology of the nanomicelles and the CMC was determined by fluorescence spectroscopy. Adopted PLGA-PEG-RA nanomicelle exhibited PS of 160 ± 9.13 nm, PDI of 0.20 ± 0.05, ZP of -24.9 ± 4.03 mV, EE of 83.9 ± 3.61%, MRT of 3.28 ± 0.35 h, and CMC value of 25.7 μg/mL. Cytotoxicity of the targeted nanomicelles on HepG2 and HT-29 cell lines was significantly higher than that of non-targeted nanomicelles and the free drug. These results suggest that PLGA-PEG-RA nanomicelles could be an efficient delivery system of irinotecan for targeted therapy of colorectal cancer and hepatocellular carcinoma.
为了开发有效的治疗方法，评估了聚（乳酸-共-乙醇酸）-聚乙二醇-视黄酸（PLGA-PEG-RA）聚合物胶束用于伊立替康靶向递送至肝癌（HepG2）和结直肠癌细胞系（HT-29）的潜力。PLGA-PEG-RA 通过 PLGA 与 NH2-PEG-NH 的酰胺反应合成，然后通过傅里叶变换红外光谱（FTIR）和核磁共振（1H NMR）光谱确认 PLGA-PEG-NH 与 RA 的反应。采用薄膜水化法制备载伊立替康的纳米胶束，并通过 Taguchi 设计评估各种制剂变量对其粒径（PS）、多分散指数（PDI）、Zeta 电位（ZP）、包封效率（EE）和平均释放时间（MRT）的影响。TEM 用于观察纳米胶束的形态，通过荧光光谱法测定 CMC。采用的 PLGA-PEG-RA 纳米胶束的 PS 为 160±9.13nm、PDI 为 0.20±0.05、ZP 为-24.9±4.03mV、EE 为 83.9±3.61%、MRT 为 3.28±0.35h 和 CMC 值为 25.7μg/mL。靶向纳米胶束对 HepG2 和 HT-29 细胞系的细胞毒性明显高于非靶向纳米胶束和游离药物。这些结果表明，PLGA-PEG-RA 纳米胶束可以作为伊立替康的有效递药系统，用于结直肠癌和肝癌的靶向治疗。
