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 degrees C, 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) min(-1) at the first minute followed by 0.4% (drug lost) min(-1) during the next hour. When incubated in plasma at 37 degrees C, the HSPC:Chol:DSPG formulations bounded a high amount of plasma proteins: r=2400 microg plasma protein per micromol total lipid.
Morilla
M J
MJ
Laboratorio de Diseño de Transportadores de Drogas, Universidad Nacional de Quilmes, Roque Saenz Peña 180, Bernal B1876BXD, Buenos Aires, Argentina.
Benavidez
P
P
Lopez
M O
MO
Bakas
L
L
Romero
E L
EL
D002626:Chemistry, Pharmaceutical; D008081:Liposomes; D009593:Nitroimidazoles / Q000737:chemistry* / Q000493:pharmacokinetics*; D013678:Technology, Pharmaceutical / Q000379:methods*
D008081:Liposomes; D009593:Nitroimidazoles; C009999:benzonidazole