Membrane material ratio influence to the stability of ferric citrate liposome

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 rotary- evaporated 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 pH 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 pH 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 i n vivo , and establish the basis for the application of iron liposomes.