Preparation Of Honokiol Delivery And Their Study Of Inhibiting Vascular Restenosis

OBJECTIVE : Screening of appropriate drug deliveries to load honokiol,and examined the pharmacodynamics and the molecular mechanism of inhibiting vascular restenosis.MDTHODS: Three drug deliveries were selected in this study:liposome,micelle,mesoporous silica nanoparticles(MSNPs).The deliveries loaded drug and form honokiol-deliveries.The physicochemical properties of the deliveries were investigated and then screen the optimal carries of encapsulated honokiol and effective concentration.The effect of honokiol-deliveries on the proliferation and migration of VSMCs was measured by flow cytometry and transwell assay;Related molecular mechanism of inhibition of VSMCs proliferation by honokiol-deliveries was detected by the RT-PCR、Western Blot and IF;A balloon injury model of the common carotid artery in rats was established,and then the pharmacodynamics and the mechanism of inhibiting vascular restenosis were investigated by periadventitial application of honokiol-deliveries in hydrogel.RESULTS: MSNPs is the best carrier for loading honokiol;HNKMSNPs can significantly inhibit the proliferation and migration of VSMCs at concentrations range from 80 μ M to 120 μ M(P < 0.05);The mechanism of inhibiting VSMCs proliferation may be related the inhibition of TGF-β-Smad2/3 phosphorylation and ERK1/2 expression(P< 0.05);local delivery HNK-MSNPs can inhibit intimal thickening and the progress of common carotid artery restenosis after balloon injury(P < 0.05),the mechanism may be related to the TGF-β--Smad2/3--ERK1/2signaling pathway.CONCLUSIONS: MSNPs can effectively encapsulate honokiol and improve the pharmacology of honokiol in inhibiting vascular restenosis.