Study On Protein Drug Delivery System Based On Liposomes Technology

Liposomes have proved to be biodegradable, nontoxic and do not elicit an immune response. As a drug deliver system, it has been extended to enhance the drug efficacy and potency, reduce toxicities of encapsulated drugs and target specific tissue sites. Multivesicular liposomes (MVLs) prepared by multiple emulsion method are distinguished from traditional liposomes by the characteristic structure and composition. While traditional liposomes are liposomes with a single bilayer surrounding an aqueous compartment or with concentric lipid bilayers, MVLs are composed of non-concentric multiple lipid layers and have more envelopment volume and bigger granularity. It has been suggested that the non-concentric nature of the arrangement of lipid layers confers an increased level of stability and longer duration of drug release. But the same as traditional liposomes, it has proved to be unstable in vivo or in vitro and cleared easily. At the same time, it is passive to capture drug during preparation. For a water-solubility protein, low encapsulation efficiency is another problem to save for. Furthermore, after purification of MVLs, it is likely to make much more unencapsulated protein lost, and purification of MVLs itself is a more complicated process.Microencapsulation is a powerful technique in the field of drug delivery system. A great deal of research is directed towards studying the use of various microencapsulation systems for this purpose. This study investigates the use alginate (Alg) microencapsulation MVLs and unencapsulated protein together to found a new type of protein delivery system (MVLs-Alg). Due to their good material characteristics and mild preparation processes, MVLs-Alg will be a more potential drug delivery carrier for protein or peptide. As a potential carrier for protein or peptide, those questions such as high encapsulation efficiency, uniform size distribution, good release performance and change of protein structure and biological activity are lack of the illustrative and quantitative understanding. Combinative mechanism between MVLs with Alg is not investigated, the same as property and stability of MVLs-Alg. Aiming at these problem mentioned above, combined two technologies of liposomes and microencapsulation, a new type of drug delivery system of protein, namely MVLs-Alg, was developed. In the dissertation, preparation processes of MVLs-Alg were optimized. Furthermore, property and stability of MVLs-Alg, release performance and combinative mechanism between MVLs with Alg were investigated, and change of structure and...