UPR 4301 CBM, CNRS, NMNS department, University of Tours, Tours, France.
Laboratoire Biologie Cellulaire et Microscopie Electronique, Faculty of Medicine, University of Tours, Tours, France.
J Liposome Res. 2024 Dec;34(4):547-561. doi: 10.1080/08982104.2024.2321528. Epub 2024 Mar 8.
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% ). 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）通过改善缺氧肿瘤环境，并减少对癌症生长至关重要的生物分子的合成，显示出在癌症治疗中有抗肿瘤特性。然而，作为一种口服药物，Met 的生物利用度低，肾脏清除率快。因此，本研究的目的是将 Met 载体化到三阴性乳腺癌（TNBC）的脂质体中，与其他类型的乳腺癌相比，目前 TNBC 缺乏治疗选择。通过采用双层设计实验方法（最小运行分辨率 V 特征设计和 Box-Behnken 设计）来增加 Met 药物载药量（通常对于亲水性分子而言，载药量极低），将 Met 载体化到脂质体中。成功实现了 Met 载脂质体的优化合成，载药量为 190mg/g（19%）。最佳的 Met 脂质体的粒径为 170nm，PdI（多分散指数）<0.1，表面带负电荷（-20mV），在 pH7.4 时可实现 Met 的持续释放。该脂质体 Met 递药系统在数月内稳定，由于封装药物的存在，成功地降低了 TNBC 细胞的增殖。本研究是首次使用两种设计实验方法通过薄膜水化来制备脂质体的报告之一，旨在提高 Met 的载药量。
