Abstract:

The objectives of the present study were to prepare stealthy etoposide proliposomes and study the pharmacokinetics in rabbits. Blank stealthy liposomes were prepared by film dispersion method. Stealthy etoposide liposomes were prepared by using the ammonium sulfate gradient loading procedure. Vacuum freeze-drying technique was used to dry stealthy etoposide liposomes. Encapsulation efficiency of stealthy etoposide proliposomes was determined by Sephadex chromatography. The morphology was observed by transmission electronic microscope. The particle size and zeta potential were measured by using electrophoretic light scattering technology. The pharmacokinetics in rabbits was evaluated by comparison with etoposide injection and conventional liposomes, respectively. Mean encapsulation efficiency of stealthy etoposide proliposomes was 83.92% ± 3.65% (n = 3). The liposomes were round or oval. Mean particle size was (124.5 ± 26.9) nm, and zeta potential was (-39.50 ± 1.04) mV. Following intravenous injection administration at a dose of 1.5 mg/kg etoposide, the three kinds of etoposide preparations were fitted with the two-compartment model. T1/2 β and AUC values of stealthy etoposide proliposomes were (19.26 ± 3.16) h and (26.04 ± 3.53) μg/h/mL, respectively. T1/2 β and AUC values of etoposide injection were (0.94 ± 0.21) h and (0.98 ± 0.26) μg/h/mL, respectively. T1/2 β and AUC values of conventional liposomes were (7.99 ± 1.36) h and (11.65 ± 1.70) μg/h/mL, respectively. Results indicated that the stealthy etoposide proliposomes could significantly extend the duration of etoposide in blood circulation.

Key words: Etoposide, Etoposide, Stealthy proliposomes, Stealthy proliposomes, High performance liquid chromatography, High performance liquid chromatography, Pharmacokinetics, Pharmacokinetics, ,