Electrosprayed Minocycline Hydrochloride-loaded Microsphere/SAIB Hybrid Depot For Periodontitis Treatment

Minocycline hydrochloride(MINO)has been one of the most frequently used antibiotics in the treatment of periodontitis due to its antibacterial activity and osteogenesis effects,however,high levels of MINO administered during the treatment halt the formation of new bone.Therefore,the current study aims to prepare a MINO-microspheres/sucrose acetate isobutyrate(SAIB)hybrid depot to reduce the burst release of MINO and ensure antibacterial and osteogenesis effects of MINO in the treatment of periodontitis.Firstly,in our study,the MINO-loaded microspheres(MINO-microspheres)were prepared by electrospray,and characterized using scanning electron microscopy(SEM),contact angle measurement,Fourier transform infrared spectroscopy(FTIR),and laser scanning confocal microscopy(LSCM),meanwhile,their drug release and degradation properties in vitro were also determined.Then,the microspheres were encapsulated into sucrose acetate isobutyrate(SAIB)to form MINO-microspheres/SAIB(MINO-M-SAIB)hybrid depot,and the drug release performance and porosity of the depot were determined,meanwhile,the binding mode between the microspheres and SAIB was analyzed by FTIR.Finally,in the model of ligatured-induced periodontitis in SD rats,the potential of MINO-M-SAIB hybrid depot for the treatment of periodontitis in vivo was evaluated by pharmacodynamic evaluation,microcomputed tomography(micro-CT),histology and immunohistochemistry analysis.The results showed uniform microspheres,approximately 5 μm size,with a slightly rough surface,good monodispersity,homogeneous drug distribution,good biodegradability and different MINO loading(10%,12%,and 14%)were prepared.Moreover,the FTIR results also showed that MINO was successfully encapsulated in microspheres and its chemical structure has not been changed.Then,after the microspheres with different drug loading(10%,12%,14%)were encapsulated into SAIB to form hybrid depots,the burst release significantly decreased from66.18% to 2.92%,from 71.82% to 3.82%,and from 73.35% to 4.45%,respectively,and the release from all the hybrid depots lasted for 77 days.In addition,the FTIR results showed that the combination of microspheres and SAIB belonged to physical blending.Finally,in the model of ligatured-induced periodontitis in SD rats,the MINO-M-SAIB hybrid depot not only significantly increased the alveolar bone height and bone volume but also reduced the inflammation of the periodontal tissue.Additionally,it also inhibited the expression of the receptor activator of nuclear factor-kappa B ligand(RANKL)and promoted the expression of osteoprotegerin(OPG).The above results show that the MINO-microspheres with good monodispersity can be prepared by electrospray.The MINO-M-SAIB hybrid depot can achieve an ideal MINO release behavior,and it might be promising in the treatment of periodontitis.