Dissertation > Medicine, health > Pharmacy > Pharmacy > Pharmaceutics

Preparation and Initial Investigation of TAT-doxorubicin Magnetic Liposomes

Author HuangXiangHua
Tutor XuWeiPing
School Anhui University of Chinese Medicine
Course Pharmacy
Keywords doxorubicin liposome magnetic TAT peptide blood brain barrier
CLC R943
Type Master's thesis
Year 2013
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Objective:Blood-brain barrier exists to make most of the drug does not enter thebrain, thereby increasing the difficulty of central nervous system diseases treatment.Surface-modified liposome or some special properties of liposome as drug carrier ofspecific drug transport to the appropriate organization or organ. TAT peptide-magneticLiposomes were investigated as a potential brain drug delivery system and thepreparation procedure was studied.Methods:In our study, doxorubicin(DOX) liposomes were prepared by modified filmdispersion-pH gradients.TAT was covalently conjugated with DSPE-mPEG2000forpreparing TAT loaded liposomes. The effect of liposomes on viability of humanhepatoma cell(HepG2)、cervical cancer cell (Hela) and rat glicoma cell(C6) werestudied by MTT colorimetric assay. Followed in vitro experiments there was a in vivoexperiments use the normal mice. DOX, TAT-DOX-LIP and TAT-DOX-Fe3O4-LIP(add magnetic field)were injected via the tail veins. At0.5,1,2,4, and8h after theinjection, HPLC was employed for the determination of doxorubicin concentrations inthe brain.Results: The size distributions of the experimental group were about100nm,doxorubicin encapsulation efficiencies are all over90%, stored at low temperaturesare relatively stable. The Fe3O4encapsulation efficiency of TAT-Fe3O4-DOX-LIP andTAT-Fe3O4-LIP are both over40%.The anti-proliferative activity against these tumourcells confirmed strong inhibitory effect of the liposomes modified withdoxorubicin-loaded TAT. The concentrations of doxorubicin in the brain ofTAT-Fe3O4-DOX-LIP(added magnetic field) at0.5,1,2,4,8h were6.69,13.38,8.28,5.12, and4.14times higher than those of DOX;1.44,2.05,1.89,1.58, and1.01timeshigher than those of TAT-DOX-LIP.Conclusions:The different groups of liposomes by modified film dispersion-pHgradients with characteristics of particle size controllable, well dispersion, highencapsulation efficiency. The inhibition effect of Doxorubicin loaded in TAT modified liposomes on cancer cell line was strongest. The potency of the TAT-modifiedliposome to enter the BBB appears to be related with the TAT modified and the Fe3O4magnetic targeting on the liposome.

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