Berberine (BER)-an anti-inflammatory quaternary
isoquinoline alkaloid extracted from plants-has been reported to have a variety of
biologic properties, including antileishmanial activity. This work addresses the preparation of BER-loaded
liposomes with the aim to prevent its rapid liver metabolism and improve the
drug selective delivery to the infected organs in
visceral leishmaniasis (VL). BER
liposomes (LP-BER) displayed a mean size of 120 nm, negative Z-potential of -38 mV and loaded 6 nmol/μmol
lipid. In vitro, the loading of BER in
liposomes enhanced its selectivity index more than 7-fold by decreasing its cytotoxicity to macrophages. In mice, LP-BER enhanced
drug accumulation in the liver and the spleen. Consequently, the liposomal delivery of the
drug reduced parasite burden in the liver and spleen by three and one logarithms (99.2 and 93.5%), whereas the free
drug only decreased the
infection in the liver by 1-log. The organ
drug concentrations-far from IC50 values- indicate that BER immunomodulatory activity or
drug metabolites also contribute to the efficacy. Although LP-BER decreased 10-fold-an extremely rapid clearance of the free
drug in mice-the value remains very high. Moreover, LP-BER reduced plasma
triglycerides levels.