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A multifunctional drug consisting of tetracycline conjugated with odanacatib for efficient periodontitis therapy.

ABSTRACT: The treatment of periodontitis can be very challenging due to its complex etiologies. A new pharmacologic strategy entitled "host-modulation therapy," has been introduced to improve periodontal treatment outcomes. Supposedly, a multifunctional drug with the potential for bacterial infection prevention, host-response modulation and bone healing promotion would be a promising option for periodontitis therapy, but related studies remain substantially lacking. In this study, we successfully conjugated tetracycline with odanacatib (a selective inhibitor of cathepsin K) to construct a multifunctional drug (TC-ODN). We discovered that TC-ODN could promote macrophages polarizing toward anti-inflammatory phenotype and promote osteogenesis of PDLSCs under inflammatory microenvironment. In vivo, TC-ODN could be absorbed and distributed specifically to the bone after systemic administration, and accumulation of TC-ODN increased bone mineral density in ovariectomized rats. Importantly, periodontal administration of TC-ODN could successfully promote bone healing in periodontitis rats with alveolar bone loss. The findings in our study uncovered the excellent biocompatibility and multifunction of TC-ODN, including bone-targeted accumulation, immunoregulation, anti-inflammatory activity and promotion of bone healing, which might contribute to the clinical treatment of periodontitis.

SUBMITTER: Li D

PROVIDER: S-EPMC9643870 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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A multifunctional drug consisting of tetracycline conjugated with odanacatib for efficient periodontitis therapy.

Li Dengke D Zhang Wuyang W Ye Weiliang W Liu Yuan Y Li Yuan Y Wang Yiming Y Shi Bingqing B Zheng Xueni X An Ying Y Ma Zhen Z Hu Kaijin K Zhou Hongzhi H Xue Yang Y

Frontiers in pharmacology 20221026

The treatment of periodontitis can be very challenging due to its complex etiologies. A new pharmacologic strategy entitled "host-modulation therapy," has been introduced to improve periodontal treatment outcomes. Supposedly, a multifunctional drug with the potential for bacterial infection prevention, host-response modulation and bone healing promotion would be a promising option for periodontitis therapy, but related studies remain substantially lacking. In this study, we successfully conjugat ...[more]

PMID: 36386169

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A multifunctional drug consisting of tetracycline conjugated with odanacatib for efficient periodontitis therapy.

Publications

A multifunctional drug consisting of tetracycline conjugated with odanacatib for efficient periodontitis therapy.

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