Characterization of mucoadhesive microspheres for the induction of mucosal and systemic immune responses.
In the present study, mucoadhesive polymer-dispersed microspheres (MS) were examined as a potential mucosal vaccine carrier. A major focus of the study was aimed at directly assessing the influence of antigen release and persistence in the mouse small intestine for the induction of mucosal and systemic immune responses. BALB/c mice were immunized with various forms of MS containing chicken egg ovalbumin (OVA) by administration into the duodenum. No detectable anti-OVA immune responses were observed following the administration of OVA alone or that of MS without mucoadhesive polymer (MS-0). MS-10 containing 10% mucoadhesive polymer rapidly released OVA and hardly induced anti-OVA antibody responses in either serum or fecal extracts. In contrast, MS-8 and MS-6 (with 8 and 6% mucoadhesive polymer) showed controlled release of OVA, which elicited strong OVA-specific IgG and IgA responses in serum and fecal extracts, respectively. Additionally, the strongest immune responses were induced in mice immunized with MS-8, which had both the optimal release-profile of OVA and the longest persistence in the small intestine. These findings indicate that antigen movement in the small intestine is an important factor and that appropriate microsphere forms with mucoadhesive polymers might be useful candidates as mucosal vaccine carriers.
Kunisawa
J
J
Department of Biopharmaceutics, Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Suita, 565-0871, Osaka, Japan.
Okudaira
A
A
Tsutusmi
Y
Y
Takahashi
I
I
Nakanishi
T
T
Kiyono
H
H
Mayumi
T
T
D000269:Adhesives; D000818:Animals; D000917:Antibody Formation; D002645:Chickens; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D018928:Immunity, Mucosal; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011108:Polymers; D014612:Vaccines / Q000008:administration & dosage*
D000269:Adhesives; D004337:Drug Carriers; D011108:Polymers; D014612:Vaccines; D010047:Ovalbumin