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Complexation hydrogels as potential carriers in oral vaccine delivery systems

Yoshida, M;Kamei, N;Muto, K;Kunisawa, J;Takayama, K;Peppas, NA;Takeda-Morishita, M;

Most current vaccine preparations are in injectable forms, which are inconvenient to patients and ineffective in mucosal immunization. Therefore, most research in this field has been directed at developing ideal oral vaccines enabling the induction of both systemic and mucosal immune responses. In the present study, we examined the utility of a pH-responsive polymeric carrier, poly (methacrylic acid-g-ethylene glycol) [P (MAA-g-EG)] hydrogel, as a potential oral vaccine carrier that can protect cargo proteins in the gastrointestinal tract. Ovalbumin (OVA) and cholera toxin (CT) were first used as the model antigen and mucosal adjuvant, respectively. In vitro incorporation and releasing studies demonstrated that approximately 30% of both OVA and CT were entrapped in the P(MAA-g-EG) hydrogel, and the release of such proteins from the hydrogel to the media was pH-dependent. In vivo oral administration of an OVA-loaded hydrogel (OVA-LP) with either CT or a CT-loaded hydrogel (CT-LP) to rats increased the levels of anti-OVA IgG in the plasma. Furthermore, when CT-LP was orally administered to mice as an antigen, both anti-CT IgG in the plasma and IgA in the fecal extract were detected. These results indicated that the P(MAA-g-EG) hydrogel is a promising and useful carrier for developing oral vaccine delivery systems.