Modular self-emulsifying drug delivery platform to enhance cellular uptake activity in triple-negative breast cancer

IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutical Sciences Pub Date : 2024-12-20 DOI:10.1016/j.ejps.2024.106993
Nandini Gandhi, Shail Modi, Shailvi Soni, Terrick Andey
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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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模块化自乳化给药平台增强三阴性乳腺癌细胞摄取活性。
三阴性乳腺癌(TNBC)表现出对某些治疗(如顺铂)的耐药表型,通常需要更高的剂量,并伴有获得性肿瘤耐药、肾毒性和不同的患者反应。提出了一种自乳化给药(SEDD)配方方法来克服顺铂在TNBC中的局限性,重点是改善细胞内顺铂和控制siRNA摄取,作为双重给药的原理证明。采用拟三元相图对顺铂(o/w)乳化液和FITC-siRNA (w/o)乳化液制备了四种SEDD配方,并对其进行了优化,以促进油包水(w/o/w)乳化液的形成。采用粒径、多分散性(PDI)、表面电荷等指标对其进行表征,并进行体外实验。通过三重染色研究了载药SEDDs的细胞摄取。SEDDs显示增强内化和促进选择性TNBC细胞摄取。目前的研究是通过SEDDs平台成功共递送顺铂(小分子)和siRNA(大分子)的原理证明。
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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