Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 13 June 2024 / Approved: 14 June 2024 / Online: 14 June 2024 (09:37:05 CEST)

A peer-reviewed article of this Preprint also exists.

Lin, S.-S.; Liu, S.-J.; Chan, E.-C.; Chong, K.-Y.; Chan, Y.-S.; Tsai, T.-T.; Niu, C.-C.; Yuan, L.-J.; Yang, C.-Y.; Hsiao, H.-Y.; Hsueh, Y.-J.; Chen, C.-A.; Ueng, S.W.N. Development of a Biodegradable PLGA Carrier to Provide Wnt Agonists and Antibiotics to Meet the Requirements for Patients with Bone Infections. Pharmaceuticals 2024, 17, 1038. Lin, S.-S.; Liu, S.-J.; Chan, E.-C.; Chong, K.-Y.; Chan, Y.-S.; Tsai, T.-T.; Niu, C.-C.; Yuan, L.-J.; Yang, C.-Y.; Hsiao, H.-Y.; Hsueh, Y.-J.; Chen, C.-A.; Ueng, S.W.N. Development of a Biodegradable PLGA Carrier to Provide Wnt Agonists and Antibiotics to Meet the Requirements for Patients with Bone Infections. Pharmaceuticals 2024, 17, 1038.

Abstract

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

Keywords

polylactide–polyglycolide; vancomycin; lithium; drug delivery; WNT agonist; mesenchymal stem cells

Subject

Medicine and Pharmacology, Orthopedics and Sports Medicine

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