Preliminary Study On Multi-Functional Micelle Crossing Blood-Brain Barrier

Lauric acid modified Lysine grafted chitosan (LA-LysCS) and Cholic acid modified Lysine grafted chitosan (CA-LysCS) was synthesized through the 1-ethyl-3-(3-dimethyl-aminopropyl)-Carbo-diimide mediated reaction. Structural characteristics of these products were investigated using FT-IR, 1H-NMR, XRD.Two kinds of micelles formed by the self-assembly of the amphiphiles obtained forward were prepared in the aqueous solution through dialysis. The critical micelle concentration (CMC) was determined by the fluorescence measurement with the pyrene as a fluorescent probe. The transmission electronic microscope (TEM), laser particles size analyzer, andζpotential analyzer were employed to investigate the properties of the micelles. The results indicated that the micelles formed by the amphiphiles was a suitable drug-carrier for their stability(CMC﹤2.3×10-2mg/mL), small size(﹤100nm), and enhanced solubility of hydrophabic drug in the aqueous solution.The drug-loaded micelles were prepared with two different kinds of drugs-the indissoluble minocycline hydrochloride with the formation of physical encapsulation, while the soluble valproate grafted to the amphiphiles through chemical reaction. The drug release in vitro was inspected at 37℃60r/min in a thermostatic shaker, and the results suggest the former coincides with the Higuchi model in which diffusion is a critical factor, while the latter agrees with the Peppas model mainly controlled by the coaction of diffusion and erosion.In order to be more efficient, a layer-by-layer self-assembly micelle was prepared by the complexation of the amphiphiles and the liposome, another with a mixed surfactant micelle. The particle size of liposome decreases with the reduction of the ratio of egg phosphatidylcholine, while the mixed surfactant micelle complies with the same rule, but with the ratio of CTAB. Compared with the LBL self-assembly micelle with the endosome of mixed surfactant micelle, the liposome one was better in both size and pattern. The magnetic liposome was prepared to be complexed with the amphiphiles to produce a magnetic targeting drug carrier, after which functionlized by Folic acid and Tat oligopeptide so that a multi-functional drug carrier including passive targeting, active targeting, physical/magnetic targeting transducation for the blood-brain barrier(BBB) was obtained. The distribution of the multifunctional LBL micelle was investigated by 99Tc-labeled SPECT. The result indicated that the multifunctional LBL micelle can successfully pass the BBB and was an advanced drug carrier in the therapy of diseases in brain.