Preparation And Pharmacodynamics Study Of Austocystin D Liposomes

This study aims to reduce the toxicity and to improve the anti-tumor activity of Austocystin D(AD)by encapsulating AD into liposomes.AD-Ls were prepared by a film dispersion-ultrasonication method and characterized in vitro and in vivo compared with AD solution(AD-Sol)formulation.The preparation prescriptions and conditions were optimized in single factor experiments.Sephadex G-25 column was used to determine the encapsulation efficiency(EE).In vitro release of AD from liposomes was measured by the dialysis bag diffusion technique.Pharmacokinetics and tissues distribution of AD-Ls and AD-Sol were studied.The in vivo anti-tumor efficacy of AD-Ls was also investigated.The obtained liposomes had a particle size of 71.26±6.43 nm,zeta potential of-9.9± 1.8 mV and encapsulation efficiency of 83.74±1.26%.AD could continuously release from liposomes for about 72 h in vitro.AD-Ls had a higher mean retention time and a lower Cmax compared with AD-Sol and could target to liver,lung and tumor,reduce the accumulation in heart,which might reduce the toxicity and side effect.In vivo,AD-Ls were more effective on controlling the growth of tumors both in HT-29 and S180 models than AD-Sol,indicating that the activity of AD was enhanced by liposome.These results indicated that AD could be encapsulated in liposome with high encapsulation efficiency.AD-Ls not only improved the solubility,but also prolonged the retention in blood and enhanced the targeting to liver and tumor of AD.Therefore,liposome would be a promising formulation for AD,providing the possibility of further investigation.