Development of dual delivery antituberculotic system containing rifapentine microspheres and adipose stem cells seeded in hydroxyapatite/tricalcium phosphate
Open Access
- 1 January 2019
- journal article
- research article
- Published by Taylor & Francis Ltd in Drug Design, Development and Therapy
- Vol. ume 13, 373-384
- https://doi.org/10.2147/dddt.s190696
Abstract
Background: Low drug concentration in the tuberculosis (TB) lesion and bone defects or nonunion after debridement are two major problems that occur in the course of treating osteoarticular TB. Thus, the combination of drug-delivery system and bone tissue repair appears to be the most promising option for osteoarticular TB treatment. Materials and methods: Herein, we report a novel anti-TB dual delivery system based on rifapentine polylactic acid microspheres (RPMs) to treat infections, with the addition of adipose-derived mesenchymal stem cells (ASCs) seeded in hydroxyapatite/tricalcium phosphate (HA/TCP) to promote bone formation. Cell proliferation, osteogenesis, and apoptosis were performed to investigate the effects of rifapentine on ASCs. The RPMs were synthesized by emulsion-solvent evaporation method, and then the monolayer composite (ASC + RPM) and three-dimensional (3D) composite scaffold (ASC + RPM + HA/TCP) were constructed, respectively. The alkaline phosphatase (ALP) activity and real-time PCR were used for determining the osteogenic differentiation. The concentrations of rifapentine resulting from the composites were detected. Results: The results showed that rifapentine has no influence on ASCs proliferation and osteogenesis when the drug concentration was below 20 µg/mL, which was significantly higher than minimal inhibitory concentration. The drug loading and encapsulation efficiency of RPMs were 40.56%±2.63% and 70.24%±2.18%, respectively. The proliferation of the cells in monolayer was higher than that in 3D composite, and the addition of RPMs slightly increased the proliferation. The ALP activity and gene expression of osteocalcin and osteopontin were higher in the 3D composite than those in the monolayer. Good biocompatibility was observed by microscopic image and H&E stain. The release tests revealed that the 3D composite exhibited sustained release profiles of rifapentine for 76 days. The dual delivery systems in 3D composite could moderate the burst release and extend the length of release time when compared to single delivery in monolayers. Conclusion: In conclusion, such dual delivery antituberculotic scaffold represents a potential new strategy for TB infections and bone defects.Keywords
This publication has 23 references indexed in Scilit:
- Surgical management for multilevel noncontiguous thoracic spinal tuberculosis by single-stage posterior transforaminal thoracic debridement, limited decompression, interbody fusion, and posterior instrumentation (modified TTIF)Archives of orthopaedic and trauma surgery, 2012
- Osteogenesis of mineralized collagen bone graft modified by PLA and calcium sulfate hemihydrate: In vivo studyJournal of Biomaterials Applications, 2012
- Formulation and in vitro characterization of inhalable rifampicin-loaded PLGA microspheres for sustained lung deliveryInternational Journal of Pharmaceutics, 2011
- Development of PLGA-Based Injectable Delivery Systems For Hydrophobic FenretinidePharmaceutical Research, 2010
- Isolation, characterization and osteogenic differentiation of adipose-derived stem cells: from small to large animal modelsCell and tissue research, 2009
- Measurement of the concentration of three antituberculosis drugs in the focus of spinal tuberculosisEuropean Spine Journal, 2008
- Tuberculosis of the SpineClinical Orthopaedics and Related Research, 2007
- One-stage Surgical Management for Multilevel Tuberculous Spondylitis of the Upper Thoracic Region by Anterior Decompression, Strut Autografting, Posterior Instrumentation, and FusionJournal of Spinal Disorders & Techniques, 2007
- Donor Site Morbidity After Anterior Iliac Crest Bone Harvest for Single-Level Anterior Cervical Discectomy and FusionSpine, 2003
- Comparison of activities of rifapentine and rifampin against Mycobacterium tuberculosis residing in human macrophagesAntimicrobial Agents and Chemotherapy, 1995