Dina M. Gaber , Sherihan S. Ibrahim , Ashraf K. Awaad , Yasmine M. Shahine , Salma Elmallah , Hebatallah S. Barakat , Noha I. Khamis
{"title":"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","authors":"Dina M. Gaber , Sherihan S. Ibrahim , Ashraf K. Awaad , Yasmine M. Shahine , Salma Elmallah , Hebatallah S. Barakat , Noha I. Khamis","doi":"10.1016/j.ijpx.2024.100249","DOIUrl":null,"url":null,"abstract":"<div><p>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. <em>In vitro</em> 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, <em>In vivo</em> 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 <em>p <</em> <em>0.001</em> with superior activity for lactoferrin-decorated formulation.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"7 ","pages":"Article 100249"},"PeriodicalIF":5.2000,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000215/pdfft?md5=f75da30078fb3cbd4ab1268e1bef84ed&pid=1-s2.0-S2590156724000215-main.pdf","citationCount":"0","resultStr":"{\"title\":\"A drug repurposing approach of Atorvastatin calcium for its antiproliferative activity for effective treatment of breast cancer: In vitro and in vivo assessment\",\"authors\":\"Dina M. Gaber , Sherihan S. Ibrahim , Ashraf K. Awaad , Yasmine M. Shahine , Salma Elmallah , Hebatallah S. Barakat , Noha I. Khamis\",\"doi\":\"10.1016/j.ijpx.2024.100249\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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. <em>In vitro</em> 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, <em>In vivo</em> 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 <em>p <</em> <em>0.001</em> with superior activity for lactoferrin-decorated formulation.</p></div>\",\"PeriodicalId\":14280,\"journal\":{\"name\":\"International Journal of Pharmaceutics: X\",\"volume\":\"7 \",\"pages\":\"Article 100249\"},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-04-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2590156724000215/pdfft?md5=f75da30078fb3cbd4ab1268e1bef84ed&pid=1-s2.0-S2590156724000215-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Pharmaceutics: X\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2590156724000215\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Pharmaceutics: X","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590156724000215","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
期刊介绍:
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The International Journal of Pharmaceutics is the second most cited journal in the "Pharmacy & Pharmacology" category out of 358 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.