【摘要】 采用薄膜旋转蒸发法制备了3种膜材比（卵磷脂与胆固醇质量比为8:1,10:1,12:1）的柠檬酸铁脂质体（FAC-Lip）.采用电导法测定了FAC-Lip的相变温度（T_m）、凝聚速率常数(K_co)、凝聚活化能(E_co),考察膜材比对其稳定性的影响;通过测定油-水分配系数(P_o/w)和脂质体-水分配系数(P_lip/w)随p H的变化趋势,考察药物FAC与脂质体膜的相互作用力类型.结果表明,随膜材比例增大,T_m略有减小,K_co先减小后增大,E_co先增大后减小,膜材比为10:1时FAC-Lip的稳定性最好;随体系p H的升高,lg P_o/w减小而lg P_lip/w增大,说明药物与脂质体膜的作用力中以氢键、静电力为主,疏水作用为辅.更多还原

【Abstract】 Iron is one of the essential trace elements, participating in many biological metabolism processes and playing an important role in maintaining the body’s normal activities. Iron deficiency can lead to iron deficiency anemia（IDA）. The conventional iron agent such as ferric citrate（FAC） has many disadvantages, such as poor taste, weak stability and low bioavailability. Liposomes are artificial bilayer membranes with similar structures as cellular membranes. They have non-toxic and non-immunogenic properties and can be used as carriers for drugs, plasmids, peptides, proteins, viruses and bacteria. Our previous work has confirmed that the ferric citrate liposomes（FAC-Lip） possessed sustained release time, improved absorption rate and good bioavailability. However, liposomes are unstable thermodynamic systems and are easy to cause the leakage of drugs during the storage process. Therefore, how to obtain the drug loading liposome with high stability is worth to study. In this work, three kinds of ferric citrate liposomes with different membrane material ratios（the mass ratios of lecithin to cholesterol were 8:1, 10:1 and 12:1, respectively） were prepared by the rotaryevaporated film-ultra sonication to investigate the influence of membrane material ratio on the stability of FAC-Lip. The phase transition temperature（T_m）, aggregate rate constant(K_co) and coagulation activation energy(E_co) were measured by electrical conductance method to determine the properties of FAC-Lip. The variety trends of oil/water partition coefficient(P_o/w) and liposome/water partition coefficient(P_lip/w) along with p H changes were also measured to determine the types of interaction force between the drug（FAC） and liposome’s membrane. Our results showed that, with the increase of membrane material ratio（from 8:1 to 12:1）, Tm changed from 53 to 52°C, suggesting that the mass of cholesterol in membrane may influence the stability of liposome; K_co decreased firstly and increased subsequently, meaning that FAC-Lip had the slowest aggregation speed at the membrane material ratio of 10:1; E_co value was the largest at the membrane material ratio of 10:1, which indicated that membrane material ratio of 10:1 had the best stability. With the p H increasing, P_o/w decreased but P_lip/w increased, which indicated that the main interaction forces between the drug and the membrane of liposome were hydrogen bonding and electrostatic force, while the hydrophobic interaction was weaker. Our study on evaluating the stability of liposomes through T_m, K_co, E_co, P_o/w and P_lip/w may guide the preparation of drug loading liposomes, predict the release property of the drug in vivo, and establish the basis for the application of iron liposomes.更多还原