Preparation Of Nimodipine Nanoliposomes And Study On Anti Parkinson

In the study, for enhancing the blood brain barrier（BBB） permeability, a newer magnetic nimodipine（NMD） nano liposomes（Fe₃O₄-NMD-Lips） were prepared and studied its neuroprotective effect and the treatment of Parkinson’s disease. First of all, the orthogonal experiment was designed to obtain NMD liposomes with high encapsulation efficiency; and then, PEG-coated Fe₃O₄ nano particles（NPs） were modified to obtain Fe₃O₄-NMD-Lips. Fe₃O₄-NMD-Lips increased the stability of NMD in the circulation of blood and could quickly and effectively across the BBB.The optimized formulation of NMD liposomes was obtained when ratios of NMD to soya lecithin, cholesterol and PEG-2000 were 1:30:1:3, and the temperature of PBS was55°C; then, NMD liposomes and the prepared PEG-coated Fe₃O₄ NPs were incubated to obtain Fe₃O₄-NMD-Lips; the encapsulation efficiency（EE） of Fe₃O₄-NMD-Lips was93.56% measured by HPLC; the images of transmission electron microscopy（TEM）demonstrated that the Fe₃O₄-NMD-Lips were spherical and monodisperse particles and the mean size was about 164 nm; the Energy-dispersive X-ray spectroscopy（EDS） and the Fourier transform infrared spectroscopy（FTIR） results showed that the PEG-coated Fe₃O₄ NPs were successfully modified on the NMD liposomes; Fe₃O₄-NMD-Lips had significant magnetic response; drug release study in vitro could be concluded that Fe₃O₄-NMD-Lips were stable and released drug slowly, thus prolonged the blood circulation time and increased its opportunity to reach the brain; in view of the microtiter tetrazolium（MTT）results, Fe₃O₄-NMD-Lips were biocompatible.Parkinson’s disease（PD） rats were established by stereotactic injection of6-hydroxydopamine（6-OHDA） in the right substantia nigra; Through the changes of factional anisotropy（FA） value of the right SN and CS in rats measured by magnetic resonance imaging（MRI）, Fe₃O₄-NMD-Lips displayed better neuroprotection than NMD solution; Fe₃O₄-NMD-Lips could increase its stability in the blood and maximum plasma concentration; the tissues distribution of NMD indicated that the combination of magnetic nanoparticles with liposomes significantly reduced the drug accumulation in other organs and improved the ability of across the BBB getting to brain; NMD concentration in brainretention was 2-fold higher in Fe₃O₄-NMD-Lips group（142.1 ng.g-1） than that of free NMD group（57.2 ng.g-1）; the results of tyrosine hydroxylase（TH） positive cells indicated that Fe₃O₄-NMD-Lips showed better more ideal neuroprotective effect. Therefore, nano magnetic drug delivery system formulated in this study was a most promising drug carrier.