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.
Acknowledgments
The authors would like to thank Louis Lantier from BioMAP team, UMR 1282, University of Tours for his help in the experiments of fluorescence microscopy, and Martin Soucé, UPR 4301, University of Tours for his guidance and advices on high performance liquid chromatography. The authors would like to thank Michèle Magistrini (UMR PRC, centre INRAE Val de Loire, France) for the gift of the extruder. The authors would also like to thank Lipoïd society for the free samples of Lipoid S100. The authors would also like to express their gratitude to Aude Mallaviale and Emmanuelle Liaudet-Coopman for the gift of the HCC38 cells (IRCM, U1194 – UM – ICM, Inserm, Montpellier, France). Daiva Vozgirdaite is aslo thankful to Labex MabImprove and Région Centre-Val de Loire for her PhD fellowship. The data were obtained with the assistance of the IBiSA Electron Microscopy Facility of the University of Tours.
Disclosure statement
No potential conflict of interest was reported by the author(s).