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Development of dual delivery antituberculotic system containing rifapentine microspheres and adipose stem cells seeded in hydroxyapatite/tricalcium phosphate

Authors Liang Q, Song X, She S, Wang Z, Wang C, Jiang D

Received 12 October 2018

Accepted for publication 19 December 2018

Published 18 January 2019 Volume 2019:13 Pages 373—384

DOI https://doi.org/10.2147/DDDT.S190696

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Manfred Ogris


Qiuzhen Liang, Xinghua Song, Shengli She, Zhen Wang, Chong Wang, Dawei Jiang

Department of Orthopaedics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China

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: tuberculosis, rifapentine, drug delivery, release system, scaffold, tissue engineering


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