Composite inclusion complexes containing hyaluronic acid/chitosan nanosystems for dual responsive enrofloxacin release

In order to overcome treatment difficulty of S. aureus infections, a pH/hyaluronidase dual responsive enrofloxacin-cyclodextrin (β-CD) inclusion complexes (IC) containing hyaluronic acid/chitosan (HA/CS) self-assemble composite nanosystems covered by poloxamer 188 (F68) was firstly explored for targeted “on-demand” delivery. The FTIR, DSC and PXRD showed that enrofloxacin was embedded into IC and then distributed into F68 coating nanogels formulated by electrostatic interaction between CS and HA. The optimal nanosystems of 118.8 ± 30.7 nm showed excellent stability and responsive release in the acid medium, hyaluronidase containing medium, and LB broth medium where S. aureus present. The nanosystems displayed strong surface adsorption on S. aureus and enhanced activity against S. aureus. It had stronger sustained release than the polymeric nanoparticles formulated by entrapping of IC into F68 and the single HA/CS nanogels. This study provides a promising multi-functionalized nanosystems to overcome the treatment challenge of S. aureus and other bacterial infections.