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Study On Degradable PEI Based Vaccine Delivery System

Posted on:2017-07-29Degree:MasterType:Thesis
Country:ChinaCandidate:W Y YanFull Text:PDF
GTID:2404330590490150Subject:Pharmaceutical
Abstract/Summary:PDF Full Text Request
Cancer vaccine is an important means of cancer immunotherapy.Tumor Antigen vaccine aims to use tumor associated antigens to active immune system and then initiate specific cellular immunity.In our earlier study,we reported that polyethylenimine(PEI25kDa)could complex with protein antigen to form nanoparticles and improve effect of antigen cross-presentation.However,the application ofPEI25 kDa was limited by its high cytoxicity to antigen presentation cells.In this study,we utilize low molecular PEI cross-linked with disulfide linkages to synthesis a disulfide-PEI(PDP),and then formed nano vaccine vector.In this research,ovalbumin(OVA)was used as a model antigen,a range of mass ratios were selected to form PDP-OVA nanoparticles.The average size of PDP-OVA nanoparticles measured by dynamic light scattering instrument was about 100 nm to 1400 nm,and the zeta potential ranged from-16 mv to +20mv.The surface morphology of nanoparticles observed by the TEM was solid spheres.The combination ratio of PDP-OVA nanoparticles at different mass ratio detected by SDS-PAGE was between 20% and 60%.To evaluate the effect of cross-presentation,PDP-OVA nanoparicles was incubated with dendritic cells and then co-cultured with B3 Z cells,specific for the OVA257-264/MHCI complex on APC surface.The results indicated that PDP-OVA nanoparticles at a range of mass ratios could improve antigen cross presentation efficiency and reduce cytotoxicity,when compared to PEI-OVA nanoparticles.After that,poly(I:C),as an adjuvant,which can improve the mature of DC and accordingly enhance the cellular immunity response,was applied into the polyplex,some initial researches were done to select different mass ratios of PDP-OVA-poly(I:C)nanoparticles according to size,zeta potential and combination of OVA.Agarose gel was used to detect the combination of poly(I:C).Microfluidics was also used to optimize nanoparticles.Results showed that when the weight ratio of PDP,OVA and poly(I:C)was above 0.8:1:0.25,nanoparticles could equip a certain protein binding rate.Our study provided preliminary evidences that degradable PEI was more efficient in antigen cross-prosentation and lower cytotoxicity.Furthermore,we have optimized the formulation of PDP-OVA-poly(I:C)nanoparicles.More research should be done to quest if the PDP-OVA-poly(I:C)nanoparticles are superior as antigen vaccine.
Keywords/Search Tags:degradable PEI, poly(I:C), cross-presentation, cancer treatment vaccines, nanocarrier system
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