Injectable Nanosponge-Loaded Pluronic F127 Hydrogel for Pore-Forming Toxin Neutralization

Abstract

PURPOSE: Pore-forming toxins (PFTs) perform important functions during bacterial infections. Among various virulence-targeting therapies, nanosponges (NSs) have excellent neutralization effects on multiple PFTs. To enhance treatment efficacy, NSs tend to be incorporated into other biomaterials, such as hydrogels. METHODS: In the present work, red blood cell (RBC) vesicles were harvested to wrap polymer nanoparticles, leading to the formation of NSs, and the optimal Pluronic F127 hydrogel concentration was determined for gelation. Then, a novel detoxification system was constructed by incorporating NSs into an optimized Pluronic F127 hydrogel (NS-pGel). Next, the system was characterized by rheological and sustained release behavior as well as micromorphology. Then, the in vitro neutralization effect of NS-pGel on various PFTs was examined by a hemolysis protocol. Finally, therapeutic and prophylactic detoxification efficiency was evaluated in a mouse subcutaneous infection model in vivo. RESULTS: A thermosensitive, injectable detoxification system was successfully constructed by loading NSs into a 30% Pluronic F127 hydrogel. Characterization results demonstrated that the NS-pGel hybrid system sustained an ideal fluidity and viscosity at lower temperatures but exhibited a quick sol-gel transition capacity near body temperature. In addition, this hybrid system had a sustained release behavior accompanied by good biocompatibility and biodegradability. Finally, the NS-pGel system showed neutralization effects similar to those of NSs both in vitro and in vivo, indicating a good preservation of NS functionality. CONCLUSION: In conclusion, we constructed a novel temperature-sensitive detoxification system with good biocompatibility and biodegradability, which may be applied to the clinical treatment of PFT-induced local lesions and infections.

Topics & Concepts