title: Complexation hydrogels as potential carriers in oral vaccine delivery systems.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Mia
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Laboratory of Drug Delivery Systems, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, Hyogo 650-8586, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Kamei
authors.affiliation: Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Keiya
authors.initials: K
authors.lastname: Muto
authors.affiliation: Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Asagi, Saito, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.affiliation: Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Departments of Chemical and Biomedical Engineering, Department of Surgery, Dell Medical School and Division of Pharmaceutics, The University of Texas at Austin, Austin, TX 78712-0231, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Peppas
authors.affiliation: Laboratory of Drug Delivery Systems, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, Hyogo 650-8586, Japan. Electronic address: mmtakeda@pharm.kobegakuin.ac.jp.
authors.forename: Mariko
authors.initials: M
authors.lastname: Takeda-Morishita
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002772:Cholera Toxin / Q000008:administration & dosage / Q000737:chemistry; D022121:Cholera Vaccines / Q000008:administration & dosage*; D004337:Drug Carriers; D020100:Hydrogels; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D022121:Cholera Vaccines; D004337:Drug Carriers; D020100:Hydrogels; D010047:Ovalbumin; D002772:Cholera Toxin
keywords: Cholera toxin; Complexation hydrogel; Mucosal immunization; Oral vaccine; Protein delivery