Chemically-modified Inulin as a Polymeric Vaccine Carrier
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Date
2014-05
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Publisher
The Ohio State University
Abstract
The use of polymers to enhance the delivery of vaccines is a growing area of research. Microparticles formed from polysaccharides can be formulated into vaccines by encapsulating a protein target (an antigen) and an immune danger signal (an adjuvant). The adjuvant is needed since most synthesized or subunit vaccines lack the immunologic potency that the entire pathogen would stimulate. Immunostimulatory polymers such as Inulin obtained from dahlia root could be used in place of a separate adjuvant. Inulin can be used as a base material to form chemically-modified polymers, such as acetalated (Ace) or trimethylsilyl (TMS) Inulin. To this end, the degradation of chemically modified Inulin microparticles of varying reaction times and modifications was tested at pH 5 and 7.4 using a spectrophotometer. The results showed a much slower release in extracellular conditions (pH 7.4) with a burst release at pH 5, corresponding to the acidity of the phagosome of phagocytic cells, which are the gatekeepers to a vaccine-mediated immune response in vivo. Additionally, the immunostimulatory effect of Inulin microparticles was evaluated using a TNF-α ELISA and the toxicity was evaluated using an MTT assay. Macrophages were incubated with five different concentrations (1000, 500, 250, 100, 50 µg/ml) of various types of Inulin microparticles (20 min Ace-Inulin, 24 hr Ace-Inulin, TMS-Inulin). Results show that the inulin microparticles are biocompatible and display a dose-dependent increase in TNF-α production. Currently, groups of inulin microparticles loaded with ova-albumin (a sample antigen) are being tested in vivo. Blood samples are being withdrawn from mice every 2 weeks, with a final sample at the end of six weeks. These samples will be tested using antibody titers, flow cytometry, and antigen recall.
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Keywords
Inulin, Vaccines, pH-sensitivity, Chemical modifications, Adjuvants, Drug Delivery