Preparation and in Vitro Drug Release Evaluation of Vitamin A-modified Saikosaponin a/d Liposomes

PENG Ying; LEI Xiaomeng; WU Yuhuan; XIA Mingyan; WEI Xinhua; WANG Tiantian; FENG Jianfang; ZHANG Guosong

Abstract：Objective Preparation of vitamin A(VA)-modified Saikosaponin(SS)a and SSd targeted liposomes and investigation of their ex vivo drug release behavior.Methods Based on the optimal ratio of soy phospholipid CS-95,cholesterol succinyl monoester 4-[(3β)-Cholest-5-en-3-yloxy]-4-oxobutanoic acid(CHEM)and targeting ligand(DSPE-PEG-VA),the drug delivery system of VA-modified SSa/SSd liposomes was constructed by coating SSa/SSd by thin-film dispersion sonication and then piggybacking DSPE-PEG-VA on liposomes in combination with post-insertion method,using encapsulation rate as the index(VA-SSa/SSd-Lips).Transmission electron microscopy(TEM)and dynamic light scattering were used to determine the liposome morphology,particle size and potential.Fisetin precipitation was used to investigate the liposome encapsulation rate and drug loading.2%rabbit erythrocyte suspension was used to investigate the hemolysis of VA-SSa/SSd-Lips.Normal rats were injected with tail vein(1 mg/kg)VA-SSa/SSd-Lips solution,SSa/SSd-After injection of VA-SSa/SSd-Lips solution,SSa/SSd-Lips solution and SSa/SSd solution into the tail vein of normal rats,blood was collected from the orbits at different time points,and the drug concentrations of SSa and SSd in the plasma of rats at each time point were determined,and pharmacokinetic parameters were calculated using DAS 3.0 software;the in vivo fluorescence distribution of VA-DiR-Lips after tail vein injection in nude rats was observed by small animal live imager.Results The average particle size of VA-SSa/SSd-Lips was(142.43±0.60)nm,PDI was(0.31±0.052),zeta potential was(-14.15±0.74)mV,and encapsulation rate of both SSa and SSd reached more than 90%;in vitro release behavior indicated that VA-SSa/SSd-Lips had some slow release effect;in vitro The in vitro release behavior indicated that VA-SSa/SSd-Lips had a slow release effect;the in vitro hemolytic evaluation showed that the hemolytic toxicity of SSa and SSd was significantly reduced after encapsulation by liposomes;the area under the drug-time curve(Area under the curve,AUC)of SSa and SSd of VA-SSa/SSd-Lips was 1.53(SSa)and 1.99(SSd)times that of SSa/SSd solution,respectively,and the bioavailability was significantly improved;the t1/2 was 2.46(SSa)and 3.19(SSd)times higher than that of SSa/SSd solution,respectively,and the t1/2 of SSa/SSd-Lips was 0.89(SSa)and 1.25(SSd)times higher than that of SSa/SSd-Sol group,respectively.VA-DiR-Lips has good liver targeting performance in live imaging.Conclusion The particle size,encapsulation rate,drug loading capacity and ex vivo drug release behavior of the VA-modified liposomes VA-SSa/SSd-Lips designed and constructed in this study achieved the design objectives of this paper.