利用阿托伐他汀钙的抗增殖活性有效治疗乳腺癌的药物再利用方法:体外和体内评估

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Dina M. Gaber , Sherihan S. Ibrahim , Ashraf K. Awaad , Yasmine M. Shahine , Salma Elmallah , Hebatallah S. Barakat , Noha I. Khamis
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引用次数: 0

摘要

乳腺癌是女性最常见的癌症,在 2020 年导致 50 多万人死亡。传统治疗费用昂贵,副作用严重。药物再利用是一种新方法,旨在将临床批准的非抗癌药物重新定位为更新的癌症治疗药物。用于治疗高胆固醇血症的阿托伐他汀钙(ATR Ca)具有调节细胞生长和凋亡的潜力。这项研究旨在利用基于凝胶的固体脂质纳米粒子(SLNs)和乳铁蛋白(Lf)作为靶向配体,增强阿托伐他汀钙的肿瘤靶向性,从而有效治疗乳腺癌。对乳腺癌细胞株(MCF-7)进行的体外细胞毒性研究表明,与未装饰的ATR Ca-SLNs和游离药物相比,Lf装饰的ATR Ca-SLNs明显提高了2至2.5倍的抗肿瘤活性。此外,还利用小鼠艾氏乳腺癌模型进行了体内研究。Caspase-3 细胞凋亡标记物显示,使用乳铁蛋白装饰/未装饰的 ATR Ca-SLNs 组(剂量为 10 毫克/千克/天)的抗肿瘤和诱导细胞凋亡活性均优于乳铁蛋白装饰制剂组(p < 0.001)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A drug repurposing approach of Atorvastatin calcium for its antiproliferative activity for effective treatment of breast cancer: In vitro and in vivo assessment

A drug repurposing approach of Atorvastatin calcium for its antiproliferative activity for effective treatment of breast cancer: In vitro and in vivo assessment

Breast cancer, the most common cancer among women, caused over 500,000 deaths in 2020. Conventional treatments are expensive and have severe side effects. Drug repurposing is a novel approach aiming to reposition clinically approved non-cancer drugs into newer cancer treatments. Atorvastatin calcium (ATR Ca) which is used for the treatment of hypercholesterolemia has potential to modulate cell growth and apoptosis. The study aimed at utilizing gelucire-based solid lipid nanoparticles (SLNs) and lactoferrin (Lf) as targeting ligand to enhance tumor targeting of atorvastatin calcium for effective management of breast cancer. Lf-decorated-ATR Ca-SLNs showed acceptable particle size and PDI values <200 nm and 0.35 respectively, entrapment efficiency >90% and sustained drug release profile with 78.97 ± 12.3% released after 24 h. In vitro cytotoxicity study on breast cancer cell lines (MCF-7) showed that Lf-decorated-ATR Ca-SLNs obviously improved anti-tumor activity by 2 to 2.5 folds compared to undecorated ATR Ca-SLNs and free drug. Further, In vivo study was also carried out using Ehrlich breast cancer model in mice. Caspase-3 apoptotic marker revealed superior antineoplastic and apoptosis-inducing activity in the groups treated with ATR Ca-SLNs either decorated/ undecorated with Lf in dosage 10 mg/kg/day p < 0.001 with superior activity for lactoferrin-decorated formulation.

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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
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