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Study on Layered Self-Assembly Magnetic Multi-functional Drug Delivery System

Author: YangYong
Tutor: ChangJin；KangChunSheng
School: Tianjin University
Course: Materials Science
Keywords: Chitosan Magnetic liposome Layered Self-assembly Targeting Blood-Brain Barrier Epilepsy Therapy
CLC: R94
Type: Master's thesis
Year: 2007
Downloads: 105
Quote: 0
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Abstract


Various Stearic acid modified Lysine grafted chitosan(SA-LysCS) with the same degrees of substitute(DS) of Stearic acid (4.9%) and different degrees of substitute (DS) of Lysine(2.3%,4.7%,9.3%) were synthesized through the 1-ethyl-3-(3-dimethyl- a-minopropyyl)-Carbo-diimide-mediated reaction. Structural characteristics of these products were investigated using FT-IR and 1HNMR. The critical aggregation concentration(CAC) of the self-aggregate of SA-LysCS were determined by measuring the fluorescence intensity of the pyrene as a fluorescent probe, which increased with increase of DS of Lysine in the range of 1.1-5.3×10-2 mg/mL. The average particle size of self-aggregates in Physiological Saline also increased with the increase of the DS of Lysine in the range of 132.6-300.2nm.Magnetic neutral liposome had been prepared successfully from Fe3O4 nanopariticles encapsulated by liposome. These magnetic neutral liposome complexed with the self-aggregate of SA-LysCS, which were known as Layered Self-Assembly Magnetic Multi-functional Micells(LSMM),and characterized using XPS, TEM, VSM and so on. Then these LSMM were surface functionalised by Folic acid (FA) and Tat oligopeptide so that the LSMM had multi-functions including active targeting , physical/magnetic targeting transducation for the blood-brain barrier(BBB). The quantities of both FA and Tat on LSMM were tested by adopting dispersion method.The biodistribution of surface functionalised LSMM in brain, heart&lung, liver&spleen, kidney and bladder of SD normal rats was investigated by 99Tc-labeled SPECT. The functions of Folic acid, Tat and effect of action time of magnetic field had also been further investigated.Drug delivery systems carrying Sodium Valproate(VPA), called Tat-FA-LSMM, had been prepared successfully. The biodistribution proved they were successfully passed the blood-brain barrier under the magnetic field, and the brain distributing was much higher than other groups.The epileptic animal seizure modal had been established , and SD modal rats were 18 cases were divided randomly into 3 groups, Physiological Saline and Sodium Valproate(VPA) were performed in group 1 and 2 respectively, and Tat-FA- LSMM was used in group 3. The results of electroencephalograph, apoptosis test and Immunophenotype test had proved that the therapeutic efficiency of Tat-FA- LSMM were much better than that of Physiological Saline and Sodium Valproate(VPA). In sum, Layered Self-assembly Magnetic multi-functional delivery system could be applied in the gene/drug therapy of brain diseases which need cross the blood-brain barrier(BBB).

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