Mannan Loaded Biodegradable and Injectable Thermosensitive PCL-PEG-PCL Hydrogel for Vaccine Delivery

In this study, we aimed to develop a novel mannan loaded in situ gel-forming controlled protein delivery system for vaccine to improve humoral immunity. Preparation and potential application of mannan loaded biodegradable and injectable thermosensitive poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) hydrogel (M-hydrogel) was investigated. The prepared M-hydrogel is a free flowing sol at low temperature, which can be mixed with basic fibroblast growth factor (bFGF) easily, and forms a non-flowing gel at body temperature acting as in situ sustained delivery depot. Moreover, the interior morphology of bFGF-loaded M-hydrogel (bFGF-M-hydrogel) was studied, which showed porous three-dimension structure. In addition, in vitro release assay indicated that bFGF could be released from the M-hydrogel system in a controlled manner. Furthermore, in vivo experiments indicated that the immunogenicity of bFGF was improved significantly after encapsulated into M-hydrogel, which was significantly higher than that of normal saline (NS), blank hydrogel, pure bFGF, bFGF loaded hydrogel (bFGF-hydrogel), bFGF and mannan mixture (bFGF-M), and bFGF loaded Complete Freund's Adjuvant (bFGF-CFA) groups. Therefore, M-hydrogel is believed to be promising as an in situ gel-forming controlled protein delivery system for vaccine.