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Characterization of mucoadhesive microspheres for the induction of mucosal and systemic immune responses
J Kunisawa1, A Okudaira, Y Tsutusmi
1Department of Biopharmaceutics, Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Suita, 565-0871, Osaka, Japan.
Abstract:
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.
Insights
Mucoadhesive microspheres show promise as mucosal vaccine carriers. Optimal antigen release and intestinal persistence, as seen with 8% polymer microspheres, significantly enhance immune responses.
Area of Science:
- Biomedical Engineering
- Immunology
- Drug Delivery
Background:
- Mucosal vaccines require effective carriers for antigen delivery to the immune system.
- Microspheres (MS) are investigated for their potential as vaccine delivery vehicles.
- Mucoadhesive properties can enhance the retention of delivery systems in the gastrointestinal tract.
Purpose of the Study:
- To evaluate mucoadhesive polymer-dispersed microspheres (MS) as mucosal vaccine carriers.
- To assess the impact of antigen release and intestinal persistence on immune responses.
- To determine the optimal microsphere formulation for mucosal and systemic immunity.
Main Methods:
- BALB/c mice were immunized via duodenal administration of ovalbumin (OVA)-loaded microspheres with varying mucoadhesive polymer content (0%, 6%, 8%, 10%).
- Antigen release kinetics and microsphere persistence in the small intestine were monitored.
- OVA-specific IgG (serum) and IgA (fecal extracts) antibody responses were quantified.
Main Results:
- Microspheres without mucoadhesive polymer (MS-0) and with rapid release (MS-10) did not induce significant anti-OVA immune responses.
- Microspheres with controlled release (MS-8 and MS-6) elicited strong OVA-specific IgG and IgA responses.
- MS-8, exhibiting optimal OVA release and longest intestinal persistence, induced the strongest immune responses.
Conclusions:
- Antigen movement and persistence in the small intestine are critical for effective mucosal and systemic immunity.
- Mucoadhesive polymer-dispersed microspheres, particularly MS-8, represent promising candidates for mucosal vaccine delivery systems.
- Tailoring microsphere properties can optimize antigen presentation and enhance vaccine efficacy.