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已发表论文
利福喷丁负载阿仑膦酸共轭 PLGA-PEG 纳米系统的发展：一种用于骨关节结核治疗的新型骨靶向策略，具有增强的药物递送和骨再生功能
Authors Wang Z, Wei H, Qiu X, Zhao B, Yang Z
Received 30 July 2025
Accepted for publication 20 November 2025
Published 2 December 2025 Volume 2025:20 Pages 14393—14411
DOI https://doi.org/10.2147/IJN.S478893
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Lijie Grace Zhang
Zhen Wang,1– 3,* Hong Wei,4,* Xiaopeng Qiu,4 Bo Zhao,4 Ziquan Yang5
1Department of Orthopedics, South China Hospital, Medical School, Shenzhen University, Shenzhen, Guangdong, 518116, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, Guangdong, 518060, People’s Republic of China; 3Department of Orthopedics, Linfen Hospital of Shanxi Medical University, Linfen, Shanxi, 041000, People’s Republic of China; 4Department of Health Examination Center, Linfen Hospital of Shanxi Medical University, Linfen, Shanxi, 041000, People’s Republic of China; 5Department of Orthopedics, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Zhen Wang, Department of Orthopedics, South China Hospital, Medical School, Shenzhen University, Shenzhen, Guangdong, 518116, People’s Republic of China, Email 421252955@qq.com Ziquan Yang, Department of Orthopedics, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China, Email yzqsdyy@126.com
Background: The treatment of osteoarticular tuberculosis (TB) remains a significant clinical challenge, primarily due to inadequate drug delivery to bone tissues, severe bone destruction, and delayed repair processes. Conventional pharmacological therapy has limited efficacy and often necessitates surgical intervention. Thus, we developed a bone-targeted nanosystem by integrating rifapentine (RPT) and alendronate (ALN) to improve drug delivery, mitigate TB-induced bone destruction, and facilitate bone regeneration.
Methods: In this study, ALN was conjugated to PLGA-PEG-COOH utilizing the DCC/NHS method and subsequently loaded with RPT through premix membrane emulsification, resulting in the formation of the RPT/ALN-PLGA-PEG nanosystems. The physicochemical properties of the nanosystems were characterized, and its antibacterial activity, cytotoxicity, and impact on osteogenic/osteoclastic differentiation were evaluated in vitro. Bone-targeting efficacy and biodistribution were assessed using in vivo experiments. A rabbit spinal TB model was used to assess therapeutic efficacy based on inflammatory and bone turnover markers, bone mineral density (BMD), and histopathological analyses.
Results: The RPT/ALN-PLGA-PEG nanosystems exhibited a uniform size of 89 nm, excellent stability, and sustained drug-release characteristics. In vitro, the nanosystems demonstrated excellent antibacterial activity, low cytotoxicity, and the ability to suppress osteoclastogenesis while promoting osteoblast differentiation. In vivo imaging and tissue distribution studies have demonstrated that the RPT/ALN-PLGA-PEG nanosystem achieved a drug concentration in bone tissue at least 3-fold higher than that of the non-targeted nanosystem. In vivo, the bone-targeted nanosystem effectively alleviated inflammation, stabilized levels of bone resorption markers, and improved BMD, accompanied by elevated levels of osteogenic markers. Histological scores revealed complete bone regeneration in the RPT/ALN-PLGA-PEG group, whereas fibrous tissue formation was observed in the other groups.
Conclusion: The RPT/ALN-PLGA-PEG nanosystems demonstrated remarkable bone-targeting capability, sustained and potent antibacterial efficacy, and mitigation of bone destruction, coupled with the promotion of bone repair. These findings provide an innovative approach for addressing osteoarticular TB.
Keywords: bone targeting, bone regeneration, nanosystems, osteoarticular tuberculosis, alendronate
1Department of Orthopedics, South China Hospital, Medical School, Shenzhen University, Shenzhen, Guangdong, 518116, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, Guangdong, 518060, People’s Republic of China; 3Department of Orthopedics, Linfen Hospital of Shanxi Medical University, Linfen, Shanxi, 041000, People’s Republic of China; 4Department of Health Examination Center, Linfen Hospital of Shanxi Medical University, Linfen, Shanxi, 041000, People’s Republic of China; 5Department of Orthopedics, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Zhen Wang, Department of Orthopedics, South China Hospital, Medical School, Shenzhen University, Shenzhen, Guangdong, 518116, People’s Republic of China, Email 421252955@qq.com Ziquan Yang, Department of Orthopedics, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China, Email yzqsdyy@126.com
Background: The treatment of osteoarticular tuberculosis (TB) remains a significant clinical challenge, primarily due to inadequate drug delivery to bone tissues, severe bone destruction, and delayed repair processes. Conventional pharmacological therapy has limited efficacy and often necessitates surgical intervention. Thus, we developed a bone-targeted nanosystem by integrating rifapentine (RPT) and alendronate (ALN) to improve drug delivery, mitigate TB-induced bone destruction, and facilitate bone regeneration.
Methods: In this study, ALN was conjugated to PLGA-PEG-COOH utilizing the DCC/NHS method and subsequently loaded with RPT through premix membrane emulsification, resulting in the formation of the RPT/ALN-PLGA-PEG nanosystems. The physicochemical properties of the nanosystems were characterized, and its antibacterial activity, cytotoxicity, and impact on osteogenic/osteoclastic differentiation were evaluated in vitro. Bone-targeting efficacy and biodistribution were assessed using in vivo experiments. A rabbit spinal TB model was used to assess therapeutic efficacy based on inflammatory and bone turnover markers, bone mineral density (BMD), and histopathological analyses.
Results: The RPT/ALN-PLGA-PEG nanosystems exhibited a uniform size of 89 nm, excellent stability, and sustained drug-release characteristics. In vitro, the nanosystems demonstrated excellent antibacterial activity, low cytotoxicity, and the ability to suppress osteoclastogenesis while promoting osteoblast differentiation. In vivo imaging and tissue distribution studies have demonstrated that the RPT/ALN-PLGA-PEG nanosystem achieved a drug concentration in bone tissue at least 3-fold higher than that of the non-targeted nanosystem. In vivo, the bone-targeted nanosystem effectively alleviated inflammation, stabilized levels of bone resorption markers, and improved BMD, accompanied by elevated levels of osteogenic markers. Histological scores revealed complete bone regeneration in the RPT/ALN-PLGA-PEG group, whereas fibrous tissue formation was observed in the other groups.
Conclusion: The RPT/ALN-PLGA-PEG nanosystems demonstrated remarkable bone-targeting capability, sustained and potent antibacterial efficacy, and mitigation of bone destruction, coupled with the promotion of bone repair. These findings provide an innovative approach for addressing osteoarticular TB.
Keywords: bone targeting, bone regeneration, nanosystems, osteoarticular tuberculosis, alendronate