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

Author:

Lin Song-Shu123ORCID,Liu Shih-Jung4ORCID,Chan Err-Cheng5,Chong Kowit-Yu35ORCID,Chan Yi-Sheng13,Tsai Tsung-Ting136ORCID,Niu Chi-Chien13,Yuan Li-Jen7,Yang Chuen-Yung13,Hsiao Hui-Yi89ORCID,Hsueh Yi-Jen810ORCID,Chen Chung-An13,Ueng Steve W. N.136

Affiliation:

1. Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

2. Department of Nursing, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan

3. Hyperbaric Oxygen Research Lab, Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

4. Department of Mechanical Engineering, Chang Gung University, Taoyuan 333, Taiwan

5. Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan 333, Taiwan

6. College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

7. Department of Orthopaedic Surgery, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan

8. Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

9. Department of Biomedical Science, Chang Gung University, Taoyuan 333, Taiwan

10. Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

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.

Funder

National Science Council and Chang Gung Memorial Hospital, Taiwan, Republic of China

Publisher

MDPI AG

Reference35 articles.

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