XIONG Wei 1 , YUAN Lingmei 2 , WANG Liangxia 3 , QIAN Guowen 4 , LIANG Chaoyi 1 , PAN Bin 1 , GUO Ling 1 , WEI Wenqiang 1 , QIU Xunxiang 1 , DENG Wenfang 1 , ZENG Zhikui 3,5
  • 1. Graduate School, Jiangxi University of Traditional Chinese Medicine, Nanchang Jiangxi, 330004, P. R. China;
  • 2. Department of Ophthalmology, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang Jiangxi, 330006, P. R. China;
  • 3. Department of Traumatic Orthopedics, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang Jiangxi, 330006, P. R. China;
  • 4. Institute of International Innovation, Jiangxi University of Science and Technology, Nanchang Jiangxi, 330013, P. R. China;
  • 5. National Engineering Research Center of Traditional Chinese Medicine Solid Preparation Manufacturing Technology of Jiangxi University of Traditional Chinese Medicine, Nanchang Jiangxi, 330004, P. R. China;
ZENG Zhikui, Email: zengzhekui185@163.com
Mesoporous bioactive glasses; polydopamine; berberine; antibacterial property; osteogenesis
10.7507/1002-1892.202308054
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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.

Citation： XIONG Wei, YUAN Lingmei, WANG Liangxia, QIAN Guowen, LIANG Chaoyi, PAN Bin, GUO Ling, WEI Wenqiang, QIU Xunxiang, DENG Wenfang, ZENG Zhikui. Preparation of berberine-naringin dual drug-loaded composite microspheres and evaluation of their antibacterial-osteogenic properties. Chinese Journal of Reparative and Reconstructive Surgery, 2023, 37(12): 1505-1513. doi: 10.7507/1002-1892.202308054 Copy

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