Development of a Biodegradable PLGA Carrier to Provide Wnt Agonists and Antibiotics to Meet the Requirements for Patients with Bone Infections

Song-Shu Lin, Shih-Jung Liu, Err-Cheng Chan, Kowit Yu Chong, Yi-Sheng Chan, Tsung-Ting Tsai, Chi-Chien Niu, Li-Jen Yuan, Chuen-Yung Yang, HUI-YI HSIAO, Hsueh Yi-Jen, Chung-An Chen, Steve W. N. Ueng*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

Antibiotic beads can be used to treat surgical infections. In this study, polylactide–polyglycolide (PLGA) was mixed with vancomycin, the osteogenic enhancer lithium chloride (LiCl), and hot compression to form PLGA-vancomycin-LiCl delivery beads to treat bone infection. An elution method was used to characterize in vitro release characteristics of vancomycin and Li over a 42-day period. The release profiles lasted for more than 42 days for vancomycin and 28 days for Li. The concentration of vancomycin in each sample was well above the breakpoint sensitivity. Lithium cotreatment enhanced the bactericidal effect of vancomycin. Released Li and vancomycin increased the mRNA or protein expressions of osteogenic markers of mesenchymal stem cells (MSCs). In vivo, the PLGA delivery systems were implanted into the distal femoral cavities of rabbits, and the cavity fluid content was aspirated and analyzed at each time point. The released Li and vancomycin lasted more than 6 weeks, and the vancomycin concentrations were much greater than the breakpoint sensitivity. Four rabbits in each group were sacrificed at 8 weeks for histological observation. More mature bone tissue was observed in the Li treatment group. This study provides a PLGA drug delivery system to meet the requirements of patients with bone infections.

Original languageAmerican English
Article number1038
JournalPharmaceuticals
Volume17
Issue number8
DOIs
StatePublished - 06 08 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

  • WNT agonists
  • drug delivery
  • lithium
  • mesenchymal stem cells
  • polylactide–polyglycolide
  • vancomycin

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