Self-assembly Of Complexes Prepared By Protein And Polysaccharides And Its Applications

With the development of science and technology, the knowledge on different subjects is intercrossing and integrating. Nanomedicine that emerges from nanotechnology and medicine shows great potential in diagnosis and therapy. Multifunctional nanocarriers are a particularly hot topic in nanomedicine especially for anti-tumor drug delivery. The concept of self-assembly in life science was introduced into chemistry, and molecule based self-assembly offers one of the most general strategies for fabricating nanostructure materials. Nanoparticles are considered as potential drug delivery systems. These systems in general can be used to provide targeted (cellular/tissue) delivery of drugs, to improve oral bioavailability, to sustain drug effect in target tissue, to solubilize drugs for intravascular delivery, and to improve the stability of therapeutic agents against enzymatic degradation. In recent years, significant effort has been devoted to develop nanocarriers based on synthetical polymers. However, they are limited by their high cost, non-green process and health safety. On the other hand, biopolymers such as proteins and polysaccharides with good biocompatibility and biodegradability are extensively used in pharmaceutics fields, because of their natural source and binding abilities with drugs. However, up to now, there are few reports of self-assembled core-shell nanoparticles based on proteins and polysaccharides as well as their biomedical applications.This thesis contains the following two parts:Firstly, doxorubicin, bovine serum albumin (BSA) and dextran were used to fabricate doxorubicin-BSA-dextran nanoparticles. BSA-dextran conjugates were first synthesized by Maillard reaction, then doxorubicin and the conjugates were mixed together to produce doxorubicin-BSA-dextran complexes, finally the complexes were heated to obtain doxorubicin-BSA-dextran nanoparticles. Effects of variable parameters on doxorubicin-BSA-dextran nanoparticles formation were studied, and monodispersed nanoparticles with 91 nm radius were obtained under optimum conditions. Besides, the nanoparticles have a spherical shape having a BSA and doxorubicin core and dextran shell structure.The dextran on the shell makes the nanoparticles stable in pH 7.4 aqueous solution during storage, and they can pass through 0.2μm filter for asepsis. The technique used can produce a high loading capacity for doxorubicin, the largest loading amount and efficiency of doxorubicin in the nanoparticles are above 30% and 90%, respectively. In vitro release study shows a sustained release of doxorubicin from the nanoparticles, and a relatively rapider release of doxorubicin at pH 5.0 than that at pH 7.4. Most importantly, the nanoparticles can prolong the life of murine ascites hepatoma H22 tumor-bearing mice from 14.5 to 22.6 days.The secondary part focuses on exploring the possibility of using soy bean protein and soluble soybean polysaccharide complexes as emulsifier to stable the emulsion. When the pH value of the solution is below the isoelectric point of the protein, soy bean protein is positively charged while polysaccharide is negatively charged which induce the formation of electrostatic complexes in the solution. With the help of ultrasonication, the complexes can absorb on oil droplet surface and stabilize the emulsions.Effects of variable parameters on emulsion formation were studied to obtain the optimum conditions. The effects of environmental stresses, such as pH, ionic strength and storage, were investigated by light scattering, the results show the emulsion can be stable in different pH,especially in the pI of the soy bean protein. However, the long-term stability of the emulsion, when NaCl was added, had not tackled, although we used two types of soluble soybean polysaccharides. The reason is unknown at this stage.