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Published on: September 17, 2014
Development and in vitro characterization of rifapentine microsphere-loaded bone implants: a sustained drug delivery
Zhen Wang1, Xinghua Song2, Huan Yang3
1Department of Orthopeadics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
Background:
This study aimed to develop and evaluate a sustained drug delivery system for the treatment of osteoarticular tuberculosis (TB) to address the issues surrounding low drug concentration in lesions and bone defects or nonunion after debridement.
Methods:
The effects of rifapentine on the proliferation and cell cycle of bone marrow mesenchymal stem cells (BMSCs) were evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry. Rifapentine polylactic acid (PLA) sustained-release microspheres (RPSMs) were prepared through the double emulsion solvent evaporation method and investigated the antibacterial activity in vitro. In this study, two sustained drug delivery systems were prepared by integrating RPSMs and BMSCs into hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) or allogeneic bone. We evaluated these drug delivery systems for dynamics of drug release and osteogenic ability by in vitro release test, alkaline phosphatase (ALP) and alizarin red staining, and real-time PCR.
Results:
The results showed that rifapentine concentrations up to 45.0 μg/mL had no effect on cell proliferation and cell cycle. The encapsulation and drug loading efficiency of the fabricated RPSMs were 78.11%±1.16% and 35.57%±0.85%, respectively. The RPSMs had uniform particle size distribution and a long-term anti-bacterium effect. The HA/β-TCP-implanted drug delivery system was found to be more effective in reducing the burst release and having a longer duration of sustained release and retention compared to allogeneic bone. The ALP and alizarin red staining and real-time PCR results showed that it had excellent osteoconductive and osteoinductive properties.
Conclusions:
In conclusion, the sustained drug delivery system with HA/β-TCP as scaffold material represents a potential new strategy for TB infections and bone defects.
