Biodegradable Polymers As Vaccine Delivery Systems For Immunization Research

Immunization is an economical and effective way to prevent and control diseases.Along with the wide spread of various diseases,the demand of vaccines is also increasing.Vaccines applied in clinical practice must have two key properties: efficacy and safety.However,the efficacy of vaccines is often compromised in order to guarantee safety for the first place.As a result,we could use immune adjuvant to improve the efficacy of vaccines.In this article,we studied the immune effect of thermo-sensitive hydrogel poly(lactic-co-glycolic acid)–poly(ethylene glycol)–poly(lactic-co-glycolic acid)and poly(glutamic acid-g-choline phosphate)as vaccine delivery systems.1.Evaluation of immune effect of thermo-sensitive hydrogel PLGA-PEG-PLGA delivery ovalbumin for intramuscular immunizationPLGA-PEG-PLGA is a kind of thermo-sensitive hydrogel which has displayed excellent physiochemical characteristics as drug/gene delivery systems,such as good biocompatibility and biodegradation,sol-gel transition along with temperature increase,and hence convenient injectable administration.In this study,we explored the PLGA-PEG-PLGA sol-gel transition temperature is around 32°C.First,in vitro release experiments showed that PLGA-PEG-PLGA hydrogel could release ovalbumin in a sustainable way.From the fluorescence in vivo living imaging experiments,the concentration of 50-200 mg/m L PLGA-PEG-PLGA formulations could release ovalbumin in a more sustainable manner.Immunohistochemistry results showed that PLGA-PEG-PLGA hydrogel could increase the availability of ovalbumin in the spleens of immunized mice.The intramuscular immunization results showed that the 50-200 mg/m L of PLGA-PEG-PLGA vaccine as delivery system could significantly improve Ig G antibody titers.In addition,the 200 mg/m L PLGA-PEG-PLGA formulations could significantly increase the secretion of Th1 and Th2 cytokines.From in vitro splenocyte proliferation assay,50-200 mg/m L of PLGA-PEG-PLGA formulations all initiated significantly higher splenocyte activation.These results indicate that the thermo-sensitive hydrogel PLGA-PEG-PLGA owns promising potential as an intramuscular vaccine delivery system.2.Evaluation of immune effect of PGA-CP delivery ovalbumin for intranasal immunizationPGA-CP is a biopolymer material which is positively charged and own excellent biodegradability.In this paper,we chose PGA-CP as a vaccine delivery system for intranasal immunization.The cytotoxicity assay showed that PGA-CP has low cytotoxicity,and the cell viability could reach above 80% at the concentration of PGA-CP at 2 mg/m L.From the immunohistochemical experiment results,different concentrations of PGA-CP as a vaccine delivery system for intranasal immunization could protect antigen from removing by nasal mucociliary.The results of Ig A antibody titers in nasal and vagina lavage fluid showed that PGA-CP/OVA formulations with a mass ratio of 5:1 could improve Ig A titers compared with negative control.In addition,PGA-CP/OVA formulations with a mass ratio of 5:1 could significantly increase the secretion of cytokines IL-10 and IL-12,and significantly increased the proliferation of lymphocyte.These results showed that PGA-CP with higher concentration has more potential as a mucosal delivery system.