LIPOSOMES LOADED WITH BERBERINE HYDROCHLORIDE: DEVELOPMENT, OPTIMISATION AND IN VITRO CITOTOXICITY

In continuing our studies on the development of nanoliposomes [1], we now report three formulations containing different amount of cholesterol for the delivery of berberine hydrochloride (BRB). BRB, an isoquinoline alkaloid, is present in many plants and it is characterized by several pharmacological activities [2]. However, BRB shows low bioavailability, so we evaluated whether liposomes could be used for the delivery of the compound. In the present study we also evaluated cellular uptake of liposomes loaded with BRB using K562 and MCF-7 cells line by flow cytometry. Polydispersion of the vesicles showed values from 0.16 to 0.32, indicating the homogeneity of the formulations. Regarding ζ-potential, all vesicles displayed a negative surface charge ranging from -32.3 to -40.3 mV. The EE% values of these liposomes ranged from 21 to 41%. TEM analyses revealed that all formulations had a spherical shape, with a good size distribution. Cellular uptake studies using K562 cells showed fluorescence ratio from 66 to 51; the assays conducted using MCF-7 cells showed fluorescence ratio from 96 to 39. Liposomes with low concentration of cholesterol showed the best fluorescence ratio, so this formulation was chosen for cytotoxicity studies. There was no significant difference of IC50 between free BRB and BRB-loaded liposomes. Developed vesicles could provide for an improved biopharmaceutical profile through reduced toxicity, favourable pharmacokinetic behaviour and an enhanced therapeutic index in comparison to the free drug.

[1] Leto, I, Coronnello, M, Righeschi, C, Bergonzi, M. C, Mini, E, & Bilia, A. R.ChemMedChem 2016; 11: 1745 – 1751.

[2] Ferraroni, M, Bazzicalupi, C, Bilia, A. R, & Gratteri, P. Chemical Communications 2011; 47: 4917 – 4919.