Development and in vitro characterisation of a benznidazole liposomal formulation

The purpose of this study was to find a multilamellar liposomal formulation for the antichagasic drug Benznidazole (BNZ). Different lipid matrices and organic solvents for BNZ were tested in order to obtain the liposomes with the highest g BNZ/100 g total lipid (D /TL) ratio. The best lipid matrices resulted from hydrogenated phosphatidylcholine from soybean (HSPC): Cholesterol (Chol): distearoyl-phosphatidylglycerol (DSPG) (molar ratio 2:2:1) prepared with BNZ dissolved in DMSO. Drug loading of 2 g BNZ/100 g total lipids at a total lipid concentration of 20/30 mM was obtained. Two in vitro assays on the HSPC:Chol:DSPG formulation to predict its in vivo behaviour were performed. In the first experiments, after 60 min at 1/450-fold dilution in buffer at 37 8C, the amount of drug associated to liposomes was reduced from 2 to 0.25 g BNZ/100 g total lipids at a rate of 65 % (drug lost) min1 at the first minute followed by 0.4 % (drug lost) min1 during the next hour. When incubated in plasma at 37 8C, the HSPC:Chol:DSPG formulations bounded a high amount of plasma proteins: r/2400 mg plasma protein per mmol total lipid