Engineering Bioerodible Polymers with Tailored量身定制的工程可生物降解聚合物.pptVIP

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Engineering Bioerodible Polymers with Tailored量身定制的工程可生物降解聚合物.ppt

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Single-Dose Vaccine Carrier for Modulation of Immune Response Mechanisms Matt J. Kipper1, Jennifer Wilson2, Michael Wannemuehler2, and Balaji Narasimhan1 1Department of Chemical Engineering, Iowa State University 2Department of Veterinary Microbiology and Preventive Medicine, Iowa State University 68a – AIChE Annual Meeting, November 9, 2004 Controlled Release Improves on Conventional Administration Schedules Many Controlled Release Formulations have been Marketed Polyanhydrides are Excellent Candidates for Controlled Release Polymer Chemistry and Microstructure Affects Erosion and Release Kinetics Current Vaccine Administration Schedules are Non-Ideal 700,000 neonatal deaths world-wide from tetanus Conventional injection schedules Many injections Patient compliance Controlled release technology Single injection Multiple formulations NIH Lists Single Dose Vaccines as #1 Grand Challenge in Global Health Controlled Release Formulations Offer Several Advantages for Vaccines Polyester-based (PLGA) single-dose vaccines Protective immunity possible w/single-dose (Corradin, O’Hagan) Antibody titer and isotype/subclass similar to that in alum-based systems (Corradin) Acidic/aqueous microenvironment reduces antigenicity (Schwendeman, Langer) Two Immune Response Mechanisms Offer Different Protection Research Paradigm Goal Engineer tetanus toxoid (TT)-loaded polyanhydride microspheres and study in vivo immune response Microspheres Fabricated by W/O/O Double Emulsion Non-Porous Microspheres Provide Extended Release Kinetics Polyanhydride Microspheres Induce Dose-Dependent Inhibition TT-Loaded Microspheres Provide Immunity 5 C3He/OuJ mice per group Injected IM (right quadriceps) with 2% loaded TT-loaded microspheres (0.5mg) and/or bolus of unencapsulated TT (0.5mg) Bled weekly from saphenous vein TT-specific IgG antibody titer determined by ELISA TT-Loaded Microspheres Provide Immunity 20:80TT Microspheres Provide High-Avidity Antibody 10–week serum samples tested by ELIS