Abstract
In order to attain a sustained release at targeted organs in a prolonged time which can reduce the side effects and maximize the therapeutic effect, aclarubicin (ACL) was entrap ped into liposomes of different lipid compositions using Microfluidizer, and dry liposomes were prepared by lyophilization. The dry aclarubicin-entrapped liposomes were evaluated in terms of mean particle size and size distribution, entrapment efficiency and in vitro drug release profile. The Entrapment efficiency of liposome, when the concentration of aclarubicin and lipid were 0.5 to 1.0mg/ml and $200{\mu}mol$/ml, respectively, was over 80% using Microfluidizer, in contrast to 70% of entrapment efficiency using hand-shaking method. Mean particle size and size distribution of aclarubicin-entrapped liposomes of various lipid compositions did not change considerably by the freeze drying. The range of particle size was between 80 and 200nm. Among aclarubicin-entrapped liposomes, ACL-liposome of PC/DPPC/CH0L/TA displayed the most significant sustained release. The addition of DPPC appeared to be favorable for the control of release. In general, aclarubicin entrapped in liposomes was less stable than free aclarubicin either in pH 7.4 phosphate buffer or in human plasma. Formulation I($t_{1/2}$, 20.3 hr) devoid of lipid additive was the most unstable in the phosphate-buffer solution while formulation II($t_{1/2}$, 40.7 hr) with cardiolipin was the most stable. Half lives of aclarubicin-entrapped liposomes in human plasma were 43.2, 50.7, 35.9 and 35.3 hr for formulation I. II, III and IV, respectively, in contrast to 57.8 hr for free aclarubicin.
