Development and in vitro characterization of drug delivery system of rifapentine for osteoarticular tuberculosis

Wu, Jun; Zuo, Yi Y.; Hu, Yunjiu; Wang, Jian; Li, Jidong; Qiao, Bo; Jiang, Dianming

doi:10.2147/dddt.s78407

Cited by 17 publications

(14 citation statements)

References 19 publications

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“…When the microspheres entered the sustained release phase, which is a slower process, the drug release was mainly associated with the degradation of PLGA microspheres as well as the entrance of drugs from the microspheres into the release medium via diffusion. Thus, the release rate curve rose slowly during the sustained release phase 12,14,24. In 2012, Gilchrist et al19 fabricated fusidic acid-rifampicin-loaded PLGA microspheres, and fusidic acid-rifampicin-loaded PLGA microspheres was characterized exclusively by a large initial burst release phase but minimal release thereafter, which was similar to the findings of this study.…”

Section: Resultssupporting

confidence: 84%

Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of cavitary pulmonary tuberculosis: preparation and in vitro characterization

Huang¹,

Chen²,

Liu³

et al. 2017

DDDT

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In this study, we aimed to design controlled-release microspheres for the treatment of cavitary pulmonary tuberculosis (TB) for solving the issues of poor drug delivery and short duration maintained at effective drug concentration during bronchoscopic interventional therapy. We fabricated rifapentine-linezolid-loaded poly(lactic acid-co-glycolic acid) microspheres (RLPMs) using the oil-in-water emulsion solvent evaporation method and assessed their in vitro release as well as the bronchial mucosal retention characteristics. The microspheres are spherical in shape with a circular concave on the surface. The particle size of RLPMs was 27.38±1.28 μm. The drug loading of rifapentine and linezolid was 18.51±0.26 and 8.42%±0.24%, respectively, while the encapsulation efficiencies were 55.53±0.78 and 16.87%±0.47%, respectively (n=3). During the burst release phase of the in vitro release test, 21.37%±0.68% rifapentine was released in 3 days and 43.56%±2.54% linezolid was released in 1 day. Then, both the drugs entered the sustained release phase. Finally, the cumulative percentage release of rifapentine and linezolid in 14 days was 27.61±1.52 and 51.01%±3.31%, respectively (n=3). Bronchoscopic observation revealed that the controlled-release microspheres could slowly release the drugs and retain them on the surface of bronchial mucosa of canines for 20 days. These results indicated that the fabricated microspheres exhibited a significant sustained release effect and could effectively retain the drugs on the surface of bronchial mucosa. Therefore, this study provides a theoretical and practical foundation for the development of fabricated microspheres loaded with multiple anti-TB drugs in the bronchoscopic interventional therapy of cavity pulmonary TB.

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Section: Resultssupporting

confidence: 84%

Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of cavitary pulmonary tuberculosis: preparation and in vitro characterization

Huang¹,

Chen²,

Liu³

et al. 2017

DDDT

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“…The in vitro study demonstrated that RPMs were bioactive and controlled release delivery systems, and they could effectively inhibit the growth of S. aureus (Wu et al, ). RPM‐loaded BHA/PAA was suggested to have curative effect on the treatment of rabbit chronic osteomyelitis induced by S. aureus (Yan et al, ).…”

Section: Discussionmentioning

confidence: 99%

Effect of bone‐like hydroxyapatite/poly amino acid loaded with rifapentine microspheres on bone and joint tuberculosis in vitro

Liu

Jiang

2017

Cell Biology International

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Rifapentine-loaded poly(lactic-co-glycolic acid) microspheres (RPMs)-loaded bone-like hydroxyapatite/poly amino acid (BHA/PAA) is effective in curing Staphylococcus aureus-induced chronic osteomyelitis. This study continues to investigate the effect of RPM-loaded BHA/PAA on the bacterial growth of Mycobacterium tuberculosis (MTB), cell proliferation and differentiation in MTB H37Rv-infected MG63 cells. Furthermore, whether Wnt/β-catenin signaling pathway was activated by RPM-loaded BHA/PAA was explored. We found the bactec growth index of H37Rv was significantly inhibited by RPM-loaded BHA/PAA. The MTT assay showed that RPM-loaded BHA/PAA could promote the cell proliferation of H37Rv-infected MG63 cells, as determined by MTT assay. The alkaline phosphatase (ALP) activity and the expression of runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) was examined by commercial kit and Western blot analysis to determine the effect of RPM-loaded BHA/PAA on MTB H37Rv-infected MG63 cell differentiation. It was revealed that RPM-loaded BHA/PAA could promote cell differentiation of H37Rv-infected MG63 cells. Furthermore, we found the expression of Wnt1, LDL receptor related protein 6 (Lrp6) and β-catenin was significantly increased in H37Rv-infected MG63 cells following treatment with RPM-loaded BHA/PAA, as determined by Western blot analysis. In conclusion, this study demonstrated that RPM-loaded BHA/PAA has an effective activity against MTB. RPM-loaded BHA/PAA promoted cell proliferation and cell differentiation of H37Rv-infected MG63 cells. Wnt/β-catenin signaling could be activated by RPM-loaded BHA/PAA in MG63 cells infected with H37Rv. This study demonstrated the potential value of RPM-loaded BHA/PAA in treating bone and joint TB, and suggested Wnt/β-catenin signaling may be an important pathway underlying its function.

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“…The present results were consistent with previous studies from our group (22,23) and confirmed that BHA/PAA is a good bone graft substitute material with good biological compatibility and capable of osteogenic induction. RPM was first generated by our research group (16) and preliminary experiments have characterized the physiochemical properties of RPMs. RPMs were spherical with rough surfaces.…”

Section: Discussionmentioning

confidence: 99%

“…Preparation of materials. RPMs were prepared through an oil-in-water emulsion solvent evaporation method, as previously described (16,23). Briefly, 50 mg of rifapentine (Jinan Mingxin Pharmaceutical Co., Ltd., Sichuan, China) was dissolved into the polymer solution and 200 mg of PLGA (Jinan Daigang Biomaterial Co., Ltd., Jinan, China) was dissolved in 10 ml of dichloromethane.…”

Section: Methodsmentioning

confidence: 99%

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Release characteristics of bone-like hydroxyapatite/poly amino acid loaded with rifapentine microspheres in vivo

Liu

Zhu

Jiang

2017

Molecular Medicine Reports

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Bone-like hydroxyapatite/poly amino acid (BHA/PAA) is a potential bone repair material. Rifapentine-loaded poly(lactic‑co‑glycolic acid) microspheres (RPMs) are bioactive and efficient controlled‑release delivery systems used in vitro. The aim of the present study was to investigate the in vivo drug release characteristics of RPM‑loaded BHA/PAA on a rabbit model of bone defect. RPM was combined with BHA/PAA to obtain the drug‑loaded, slow‑releasing bioactive material. Bone defects were generated in New Zealand white rabbits and the rabbits were then implanted with RPM‑loaded BHA/PAA. High‑performance liquid chromatography (HPLC) was used to determine the concentrations of rifapentine in the plasma and the local muscle tissues of the treated rabbits. Hematoxylin and eosin (H&E) staining and biochemical analyses were performed to elucidate potential side effects of RPM‑loaded BHA/PAA on the heart, liver and kidney histopathology and functions of the treated rabbits. The biocompatibility and osteogenic ability of RPM‑loaded BHA/PAA was evaluated by H&E staining. The results demonstrated that the material was completely degraded and absorbed at 12 weeks following implantation and new trabecular bone and cartilage tissues had formed. The in vivo release tests revealed that RPM‑loaded BHA/PAA exhibited sustained release profiles of rifapentine and the drug concentration in the muscle tissues remained higher than the minimum inhibitory concentration of rifapentine against Mycobacterium tuberculosis for as long as 12 weeks. In addition, RPM‑loaded BHA/PAA had no long‑term side effects to the heart, liver and kidney of the treated rabbits. In conclusion, the present study demonstrated that RPM‑loaded BHA/PAA slowly and continuously released rifapentine in vivo and exhibited no side effects on heart, liver and kidney tissues and function. Furthermore, RPM‑loaded BHA/PAA promoted new bone formation, while it was gradually degraded and absorbed. The present study provided a theoretical basis for the potential advancement in developing novel treatments for osteoarticular tuberculosis.

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Development and in vitro characterization of drug delivery system of rifapentine for osteoarticular tuberculosis

Cited by 17 publications

References 19 publications

Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of cavitary pulmonary tuberculosis: preparation and in vitro characterization

Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of cavitary pulmonary tuberculosis: preparation and in vitro characterization

Effect of bone‐like hydroxyapatite/poly amino acid loaded with rifapentine microspheres on bone and joint tuberculosis in vitro

Release characteristics of bone-like hydroxyapatite/poly amino acid loaded with rifapentine microspheres in vivo

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