{"title":"Modular self-emulsifying drug delivery platform to enhance cellular uptake activity in triple-negative breast cancer","authors":"Nandini Gandhi, Shail Modi, Shailvi Soni, Terrick Andey","doi":"10.1016/j.ejps.2024.106993","DOIUrl":null,"url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) presents with resistance phenotypes to certain therapies, such as cisplatin, often requiring higher dosing, with associated acquired tumor resistance, renal toxicity, and variable patient responses. A self-emulsifying drug delivery (SEDD) formulation approach was proposed to overcome the limitations of cisplatin in TNBC, focusing on improving intracellular cisplatin and control siRNA uptake as a proof-of-principle of dual drug delivery. Four SEDD formulations were prepared and optimized for cisplatin (o/w) emulsion and FITC-siRNA (w/o) emulsion using pseudo-ternary phase diagrams to facilitate the formation of water-in-oil-water (w/o/w) emulsions. Formulations were characterized by size, polydispersity (PDI), and surface charge and tested in vitro. Cellular uptake via triplex staining of drug-loaded SEDDs was investigated. SEDDs showed enhanced internalization and promoted selective TNBC cellular uptake. The current study is a proof-of-principle for the successful co-delivery of cisplatin (small molecule) and siRNA (large molecule) via the SEDDs platform.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"206 ","pages":"Article 106993"},"PeriodicalIF":4.3000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Pharmaceutical Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0928098724003063","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Triple-negative breast cancer (TNBC) presents with resistance phenotypes to certain therapies, such as cisplatin, often requiring higher dosing, with associated acquired tumor resistance, renal toxicity, and variable patient responses. A self-emulsifying drug delivery (SEDD) formulation approach was proposed to overcome the limitations of cisplatin in TNBC, focusing on improving intracellular cisplatin and control siRNA uptake as a proof-of-principle of dual drug delivery. Four SEDD formulations were prepared and optimized for cisplatin (o/w) emulsion and FITC-siRNA (w/o) emulsion using pseudo-ternary phase diagrams to facilitate the formation of water-in-oil-water (w/o/w) emulsions. Formulations were characterized by size, polydispersity (PDI), and surface charge and tested in vitro. Cellular uptake via triplex staining of drug-loaded SEDDs was investigated. SEDDs showed enhanced internalization and promoted selective TNBC cellular uptake. The current study is a proof-of-principle for the successful co-delivery of cisplatin (small molecule) and siRNA (large molecule) via the SEDDs platform.
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