Daiva Vozgirdaite, Katel Hervé-Aubert, Rustem Uzbekov, Igor Chourpa, Emilie Allard-Vannier
{"title":"Design, optimization, characterization, and <i>in vitro</i> evaluation of metformin-loaded liposomes for triple negative breast cancer treatment.","authors":"Daiva Vozgirdaite, Katel Hervé-Aubert, Rustem Uzbekov, Igor Chourpa, Emilie Allard-Vannier","doi":"10.1080/08982104.2024.2321528","DOIUrl":null,"url":null,"abstract":"<p><p>Recently, metformin (Met) has shown to have antineoplastic properties in cancer treatment by improving hypoxic tumor conditions, and causing reduction in the synthesis of biomolecules, which are vital for cancer growth. However, as an orally administered drug, Met has low bioavailability and rapid renal clearance. Thus, the goal of this study was to vectorize Met inside liposomes in the context of triple negative breast cancer (TNBC), which currently lacks treatment options when compared to other types of breast cancer. Vectorization of Met inside liposomes was done using Bangham method by implementing double design of experiment methodology to increase Met drug loading (minimum-run resolution V characterization design and Box-Behnken design), as it is generally extremely low for hydrophilic molecules. Optimization of Met-loaded liposome synthesis was successfully achieved with drug loading of 190 mg/g (19% <i>w/w</i>). The optimal Met-liposomes were 170 nm in diameter with low PdI (< 0.1) and negative surface charge (-20 mV), exhibiting sustained Met release at pH 7.4. The liposomal Met delivery system was stable over several months, and successfully reduced TNBC cell proliferation due to the encapsulated drug. This study is one the first reports addressing liposome formulation through thin-film hydration using two design of experiment methods aiming to increase drug loading of Met.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"547-561"},"PeriodicalIF":3.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Liposome Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08982104.2024.2321528","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/8 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Recently, metformin (Met) has shown to have antineoplastic properties in cancer treatment by improving hypoxic tumor conditions, and causing reduction in the synthesis of biomolecules, which are vital for cancer growth. However, as an orally administered drug, Met has low bioavailability and rapid renal clearance. Thus, the goal of this study was to vectorize Met inside liposomes in the context of triple negative breast cancer (TNBC), which currently lacks treatment options when compared to other types of breast cancer. Vectorization of Met inside liposomes was done using Bangham method by implementing double design of experiment methodology to increase Met drug loading (minimum-run resolution V characterization design and Box-Behnken design), as it is generally extremely low for hydrophilic molecules. Optimization of Met-loaded liposome synthesis was successfully achieved with drug loading of 190 mg/g (19% w/w). The optimal Met-liposomes were 170 nm in diameter with low PdI (< 0.1) and negative surface charge (-20 mV), exhibiting sustained Met release at pH 7.4. The liposomal Met delivery system was stable over several months, and successfully reduced TNBC cell proliferation due to the encapsulated drug. This study is one the first reports addressing liposome formulation through thin-film hydration using two design of experiment methods aiming to increase drug loading of Met.
最近,二甲双胍(Met)通过改善肿瘤缺氧状况,减少对癌症生长至关重要的生物分子的合成,在癌症治疗中显示出抗肿瘤特性。然而,作为一种口服药物,Met 的生物利用度较低,肾脏清除率较快。因此,本研究的目标是针对三阴性乳腺癌(TNBC),将 Met 载体化在脂质体中,因为与其他类型的乳腺癌相比,三阴性乳腺癌目前缺乏治疗方案。在脂质体内载体化 Met 的过程中,采用了 Bangham 方法,通过双重实验设计方法(最小运行分辨率 V 表征设计和 Box-Behnken 设计)来提高 Met 的药物载量,因为亲水性分子的载量通常极低。成功实现了载药脂质体合成的优化,载药量为 190 毫克/克(19% w/w)。最佳的 Met 脂质体直径为 170 nm,具有低 PdI(< 0.1)和负表面电荷(-20 mV),在 pH 值为 7.4 时可持续释放 Met。该脂质体 Met 给药系统在数月内保持稳定,并且由于包裹了药物,成功地减少了 TNBC 细胞的增殖。该研究首次报道了通过薄膜水合的脂质体配方,并采用了两种实验设计方法,旨在增加 Met 的药物载量。
期刊介绍:
The Journal of Liposome Research aims to publish original, high-quality, peer-reviewed research on the topic of liposomes and related systems, lipid-based delivery systems, lipid biology, and both synthetic and physical lipid chemistry. Reviews and commentaries or editorials are generally solicited and are editorially reviewed. The Journal also publishes abstracts and conference proceedings including those from the International Liposome Society.
The scope of the Journal includes:
Formulation and characterisation of systems
Formulation engineering of systems
Synthetic and physical lipid chemistry
Lipid Biology
Biomembranes
Vaccines
Emerging technologies and systems related to liposomes and vesicle type systems
Developmental methodologies and new analytical techniques pertaining to the general area
Pharmacokinetics, pharmacodynamics and biodistribution of systems
Clinical applications.
The Journal also publishes Special Issues focusing on particular topics and themes within the general scope of the Journal.