Preparation And Evaluation Lactoferrin-modified Long Cycle Nanostructured Lipid Carries For Enhanced Brain Delivery Of Nimodipine

Objective Lactoferrin(Lf)is used to modify nimodipine(NMD)long cycle nanostructure lipid carrier(Lf-PEG-NMD-NLC),The in vitro and in vivo evaluation of the Lf-PEG-NMDNLC was present.Methods The melt-ultrasound was prepared mPEG-NMD-NLC,the Box-Behnken response surface method to screen the optimal prescription of mPEG-NMD-NLC.Under the catalysis of EDCI/NHS connect Lf to NLC,the Lf-PEG-NMD-NLC of morphology,particle size,Zeta potential,coating rate,drug-polymer interactions,and in vitro release,such as appearance,colour and lustre and dispersion as an index.Optimizing the Lf-PEG-NMD-NLC freeze-drying process and freeze-drying protectant.Using transmission electron microscopy(TEM)and dynamic light scattering particle size instrument melvin on the morphology of nanoparticles,particle size and zeta potential were characterized.Dialysis method is used to investigate in vitro release.Using ultraviolet spectrophotometry(UV-vis),infrared(FTIR)and nuclear magnetic resonance hydrogen spectrum(1H NMR)identification of Lf-PEG2000-NMDNLC.The cell model of stroke was set up by means of inducing PC12 cells with Sodium Nitroprusside(SNP).Cell survival rate and protect effect of Lf-PEG-NMD-NLC on PC12 cells with SNP was determined by the MTT assay.Apoptosis was tested by flow cytometry.In vivo imaging was developed and validated for the determination of Lf modification mediate specific targeting in brain of rat.The remarkable difference in vitro and in vivo results showed that LfPEG-NMD-NLC could be one of the promising brain-targeting drug delivery system and worthy of further investigation.Results Under the optimal conditions,the designed nanoparticles showed nearly spherical particles with a mean particle size of(169.5±14.15)nm and(-15.9±0.09)mV,The EE and DL could reach up to(93.77±0.31)% and(1.43±0.02)%.An stroke cell model was built by 300?mol·L-1 of SNP.Following the incubation time increased,both the fluorescence intensity of PC12 cells treated with mPEG-C6-NLC and Lf-PEG-C6-NLC increased.At either 1h or 4h,the fluorescence intensity of PC12 cells treated with Lf-PEG-C6-NLC was obviously higher thanthat treated with mPEG-C6-NLC.After targeted modification,NMD nanoparticles protect cells apoptosis effect reduced to 19.57%,and the targeted nanoparticles treatment of early apoptosis cells percentage nanoparticles is significantly lower than normal group,further proof that targeted molecular modification can help to improve the protection effect of nanoparticles.Through Semi-quantitative fluorescent intensity results,Lf-PEG-DiR-NLC in brain of fluorescence intensity is DiR solution and mPEG-DiR-NLC 2.95 times and 1.27 times.Conclusion The animal test in vivo proved Lf-PEG-NMD-NLC enhanced time in body and showed excellently brain-targetability.Lf-PEG-NMD-NLC showing high bioavailability and long interaction time,will has broad application prospects in future.Lf-PEG-NMD-NLC can be exploited as a potential brain-targeting drug carrier both for the treatment.Overall,the present study demonstrates that the Lf-PEG-NMD-NLC possess excellent targeting ability.Thereby,it may be a promising drug delivery carrier for targeted brain.