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盐酸吉西他滨载药脂质聚合物杂化纳米粒(LPHNs)的抗肿瘤活性:体内外研究。

Antitumor activity of gemcitabine hydrochloride loaded lipid polymer hybrid nanoparticles (LPHNs): In vitro and in vivo.

机构信息

Gazi University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06330 Etiler, Ankara, Turkey.

Gazi University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06330 Etiler, Ankara, Turkey.

出版信息

Int J Pharm. 2020 Apr 30;580:119246. doi: 10.1016/j.ijpharm.2020.119246. Epub 2020 Mar 20.

Abstract

The present study demonstrated the application of gemcitabine hydrochloride (GEM) loaded lipid polymer hybrid nanoparticles (LPHNs) for the enhancement the chemotherapeutic response. GEM, which is an anti-tumor drug, is frequently utilized for the treatment of non-small cell lung cancer, breast cancer and pancreatic cancer. GEM loaded LPHNs were formed and examined for pharmacokinetic profile and in vivo anticancer activity. Modified double emulsion solvent evaporation method was employed in the preparation of the LPHNs. Cytotoxicities of the GEM loaded LPHNs formulation were evaluated on MCF-7 and MDA-MB-231 cells by MTT assays. Pharmacokinetics and in vivo anticancer efficacy studies were conducted following intraperitoneal administration in female Sprague-Dawley rats. In vivo pharmacokinetic studies in rats exhibited the advantage of the GEM loaded LPHNs over commercial product Gemko® and the GEM loaded LPHNs had longer circulation time. The half-life of GEM in LPHNs formulation was notable advanced (4.2 folds) comparing to commercial product of GEM (native). These findings indicated that GEM loaded LPHNs can be used for enhancing antitumor efficacy for breast cancer treatment.

摘要

本研究展示了盐酸吉西他滨(GEM)负载的脂质聚合物杂化纳米粒(LPHN)在增强化疗反应方面的应用。GEM 是一种抗肿瘤药物,常用于治疗非小细胞肺癌、乳腺癌和胰腺癌。制备了 GEM 负载的 LPHN 并对其药代动力学特征和体内抗癌活性进行了考察。采用改良的双重乳液溶剂蒸发法制备 LPHN。通过 MTT 法评价了 GEM 负载的 LPHN 制剂对 MCF-7 和 MDA-MB-231 细胞的细胞毒性。通过腹腔注射雌性 Sprague-Dawley 大鼠进行药代动力学和体内抗癌疗效研究。体内药代动力学研究表明,GEM 负载的 LPHN 优于商业产品 Gemko®,且具有更长的循环时间。与 GEM 的商业产品(天然)相比,LPHN 制剂中 GEM 的半衰期显著延长(4.2 倍)。这些发现表明,GEM 负载的 LPHN 可用于增强乳腺癌治疗的抗肿瘤疗效。

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