Development and in vitro characterisation of a benznidazole liposomal formulation

M. J. MORILLA, P. BENAVIDEZ, M. O. LOPEZ, L. BAKAS, E. L. ROMERO

INTERNATIONAL JOURNAL OF PHARMACEUTICS

Elsevier

Lugar: Amsterdam; Año: 2002 vol. 249 p. 89 - 99

0378-5173

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.vents 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.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.ved 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.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./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.1 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.1 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.r/2400 mg plasma protein per mmol total lipid.