Design, optimization, characterization, and in vitro evaluation of metformin-loaded liposomes for triple negative breast cancer treatmentстатья
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Дата последнего поиска статьи во внешних источниках: 17 апреля 2024 г.
Аннотация:Recently, metformin (Met) has shown to have antineoplastic properties in cancer treatment by improv
ing 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 imple
menting double design of experiment methodology to increase Met drug loading (minimum-run reso
lution 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 190mg/g (19% w/w). The optimal Met-liposomes were 170nm in diameter with low
PdI (< 0.1) and negative surface charge (-20mV), exhibiting sustained Met release at pH 7.4. The lipo
somal Met delivery system was stable over several months, and successfully reduced TNBC cell prolif
eration 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