Journal
MOLECULAR PHARMACEUTICS
Volume 14, Issue 9, Pages 3228-3237Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.7b00586
Keywords
poly(lactic-co-glycolic acid); polymer microspheres; encapsulation; vaccine delivery; calcium phosphate adjuvant; intranasal immunization
Funding
- NIH [R21 EB 08873, R01EB022563, R01AI127070, R01CA210273]
- DoD/CDMRP [W81XWH-16-1-0369]
- NSF [1553831]
- University of Michigan Rackham Merit Fellowship
- American Foundation for Pharmaceutical Education (AFPE)
- NIGMS [GM007767]
- UM Rackham
- AFPE
- Directorate For Engineering [1553831] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys [1553831] Funding Source: National Science Foundation
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Herein we describe a formulation of self encapsulating poly(lactic-co-glycolic acid) (PLGA) micro spheres for vaccine delivery. Self-healing encapsulation is a novel encapsulation method developed by our group that enables the aqueous loading of large molecules into premade PLGA microspheres. Calcium phosphate (CaHPO4) adjuvant gel was incorporated into the microspheres as a protein trapping agent for improved encapsulation of antigen. Microspheres were found to have a median size of 7.05 +/- 0.31 mu m, with a w/w loading of 0.60 +/- 0.05% of ovalbumin (OVA) model antigen. The formulation demonstrated continuous release of OVA over a 49-day period. Released OVA maintained its antigenicity over the measured period of >21 days of release. C57BL/6 mice were immunized via the intranasal route with prime and booster doses of OVA (10 mu g) loaded into microspheres or coadministered with cholera toxin B (CTB), the gold standard of mucosal adjuvants. Microspheres generated a Th2-type response in both serum and local mucosa, with IgG antibody responses approaching those generated by CTB. The results suggest that this formulation of self-encapsulating microspheres shows promise for further study as a vaccine delivery system.
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