ABSTRACT
Objective To prepare asiaticoside-loaded modified liposomes and to investigate the distribution and pharmacokinetics. Methods Different asiaticoside-loaded preparations (include solution, modified, and unmodified liposomes) were injected by tail vein in SD rats. HPLC method was used to detect the concentration of asiaticoside in the tissue and plasma samples. And the concentration-time profiles and pharmacokinetic parameters were then obtained and compared to get the variances. Results The concentration-time profiles of asiaticoside-loaded preparations guided along the single compartment model which the weight is 1/C2. The elimination half-life of asiaticoside solution and different asiaticoside liposomes were (14.52 ± 0.56), (101.35 ± 12.47), (149.82 ± 20.00), and (159.58 ± 16.46) min, respectively. The AUC of asiaticoside solution and different asiaticoside liposomes were (1 929.70 ± 159.00), (57 004.35 ± 8 710.89), (93 736.52 ± 12 710.76), and (64 737.48 ± 6 365.28) min∙μg/mL, respectively. The mass fraction of asiaticoside in each organ increased, especially in the pulmonary which increased from (4.94 ± 0.94) μg/g to (39.12 ± 12.04) μg/g. Conclusion The sustained release and targeting effects in SD rats were obvious of the asiaticoside-loaded modified liposomes.
ABSTRACT
OBJECTIVE: To investigate the brain pharmacokinetics of co-modified liposomes of α-cobrotoxin in rats after intranasal administration. METHODS: DSPE-PEG2000-Pep1 and DSPE-PEG2000-Pep2 were synthesized by Michael addition reaction. And their structures were verified by proton nuclear magnetic resonance spectroscopy (1H-NMR) and infrared spectroscopy (FTIR). Pep2(Pep1)-αCT-LP was prepared by the method of thin-film hydration and post-inserting, then its morphology, particle size, and Zeta potential were investigated. The encapsulation efficiency of liposomes was determined by ultrafiltration centrifugal method. The concentrations of αCT-LP, Pep1-αCT-LP, Pep2-αCT-LP, and Pep2(Pep1)-αCT-LP in periaqueductal gray (PAG) after intranasal administration were measured by microdialysis and the pharmacokinetical parameters were analyzed by PKSolver software. RESULTS: The structures of DSPE-PEG2000-Pep1 and DSPE-PEG2000-Pep2 were proved by 1H-NMR and FTIR. The prepared Pep2(Pep1)-αCT-LP was nearly spherical with uniform size, the mean particle size was (115.8±1.86) nm, and the Zeta potential was (-13.77±0.75) mV. Besides, the encapsulation efficiency was (32.75±1.12)%. The RESULTS ofin vivo test demonstrated that the αCT concentrations in PAG after intranasal administration of Pep2(Pep1)-αCT-LP were significantly increased compared with the groups of αCT-LP, Pep1-αCT-LP and Pep2-αCT-LP(P<0.05). Theρmax, tmax, and AUC0→∞ were (244.72±3.15) ng·mL-1, (88.01±4.19) min, (89 199.02±1 922.99) ng·min·mL-1, respectively. CONCLUSION: Pep2(Pep1)-αCT-LP can significantly increase the concentrations of αCT in periaqueductal gray, which provides a promising method for development of polypeptide agents for brain-targeting.