Preparation of berberine-naringin dual drug-loaded composite microspheres and evaluation of their antibacterial-osteogenic properties / 中国修复重建外科杂志

OBJECTIVE@#To develop a drug-loaded composite microsphere that can simultaneously release the berberine (BBR) and naringin (NG) to repair infectious bone defects.@*METHODS@#The NG was loaded on mesoporous microspheres (MBG) to obtain the drug-loaded microspheres (NG-MBG). Then the dual drug-loaded compound microspheres (NG-MBG@PDA-BBR) were obtained by wrapping NG-MBG with polydopamine (PDA) and modifying the coated PDA with BBR. The composite microspheres were characterized by scanning electron microscopy, X-ray diffraction, specific surface area and pore volume analyzer, and Fourier transform infrared spectroscopy; the drug loading rate and release of NG and BBR were measured; the colony number was counted and the bacterial inhibition rate was calculated after co-culture with Staphylococcus aureus and Escherichia coli for 12 hours to observe the antibacterial effect; the biocompatibility was evaluated by live/dead cell fluorescence staining and cell counting kit 8 assay after co-culture with rat's BMSCs for 24 and 72 hours, respectively, and the osteogenic property was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining after 7 and 14 days, respectively.@*RESULTS@#NG-MBG@PDA-BBR and three control microspheres (MBG, MBG@PDA, and NG-MBG@PDA) were successfully constructed. Scanning electron microscopy showed that NG-MBG@PDA-BBR had a rough lamellar structure, while MBG had a smooth surface, and MBG@PDA and NG-MBG@PDA had a wrapped agglomeration structure. Specific surface area analysis showed that MBG had a mesoporous structure and had drug-loading potential. Low angle X-ray diffraction showed that NG was successfully loaded on MBG. The X-ray diffraction pattern contrast showed that all groups of microspheres were amorphous. Fourier transform infrared spectroscopy showed that NG and BBR peaks existed in NG-MBG@PDA-BBR. NG-MBG@PDA-BBR had good sustained drug release ability, and NG and BBR had early burst release and late sustained release. NG-MBG@PDA-BBR could inhibit the growth of Staphylococcus aureus and Escherichia coli, and the antibacterial ability was significantly higher than that of MBG, MBG@PDA, and NG-MBG@PDA ( P<0.05). But there was a significant difference in biocompatibility at 72 hours among microspheres ( P<0.05). ALP and alizarin red staining showed that the ALP positive area and the number of calcium nodules in NG-MBG@PDA-BBR were significantly higher than those of MBG and NG-MBG ( P<0.05), and there was no significant difference between NG-MBG@PDA and NG-MBG@PDA ( P>0.05).@*CONCLUSION@#NG-MBG@PDA-BBR have sustained release effects on NG and BBR, indicating that it has ideal dual performance of osteogenesis and antibacterial property.

Tomography Study on Total Flavonoids from Rhizoma Drynariae in Promoting New Bone Formation in Distraction Osteogenesis Rat Model / 广州中医药大学学报

Objective To establish a distraction osteogenesis SD rat model for exploring the effect of total flavonoids from Rhizoma Drynariae on the quality of rat bone formation in the process of distraction osteogenesis from the perspective of tomography.Methods Twenty-four rats were randomly divided into experimental group and control group after successful modeling,and were respectively given intragastric administration with total flavonoids from Rhizoma Drynariae(in dose of 77.125 mg/kg) and saline for 8 weeks.Seven days after operation,the tibias of all the rats were given distraction at the speed of 0.2 mm for 20 days.Eight weeks after the operation,X-ray examination for all the rats was performed,and then the rats were killed for obtaining the tibia samples for Micro-CT scanning.The differences of X-ray Lane-Sandhu scores,the bone mineral density and bone mineral content were compared between the two groups.Results The X-ray Lane-Sandhu scores,the bone mineral density and bone mineral contents showed by Micro-CT scanning in the experimental group were higher than those in the control group,and the differences were statistically significant (P ＜ 0.05).Conclusion The total flavonoids from Rhizoma Drynariae can improve the quality of bone formation in the process of distraction osteogenesis in rats.