Benzydamine inhibits osteoclast differentiation and bone resorption via down-regulation of interleukin-1 expression

Son, Han Saem; Lee, Jiae; Lee, Hyein; Kim, Na-Rae; Jo, You Jin; Lee, Gong Rak; Hong, Seong Ahn; Kwon, Minjeong; Kim, Nam Young; Kim, Hyun Jin; Park, Jin Ha; Lee, Soo Young; Jeong, Woojin

doi:10.1016/j.apsb.2019.11.004

Cited by 47 publications

(40 citation statements)

References 46 publications

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“…based on SO staining and micro-computed tomography analysis. The less severe bone destruction may be an indirect result of the ability of FPC-Exo/Dex to reduce secretion of IL-1β and TNF-α, since these factors may promote the formation of osteoclasts [ 43 – 45 ]; and to promote secretion of IL-10, which can inhibit osteoclast formation. The superior therapeutic effects of FPC-Exo/Dex over the other Dex formulations may relate to its better targeting and internalization.…”

Section: Discussionmentioning

confidence: 99%

Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis

et al. 2020

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Background: Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration, serious adverse reactions during long-term administration. To achieve better treatment, reduce side effect, we here established a biomimetic exosome (Exo) encapsulating dexamethasone sodium phosphate (Dex) nanoparticle (Exo/Dex), whose surface was modified with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol) compound to attain FPC-Exo/Dex active targeting drug delivery system. Results: The size of FPC-Exo/Dex was 128.43 ± 16.27 nm, with a polydispersity index (PDI) of 0.36 ± 0.05, and the Zeta potential was − 22.73 ± 0.91 mV. The encapsulation efficiency (EE) of the preparation was 10.26 ± 0.73%, with drug loading efficiency (DLE) of 18.81 ± 2.05%. In vitro study showed this system displayed enhanced endocytosis and excellent anti-inflammation effect against RAW264.7 cells by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokine. Further biodistribution study showed the fluorescence intensity of FPC-Exo/Dex was stronger than other Dex formulations in joints, suggesting its enhanced accumulation to inflammation sites. In vivo biodistribution experiment displayed FPC-Exo/Dex could preserve the bone and cartilage of CIA mice better and significantly reduce inflamed joints. Next in vivo safety evaluation demonstrated this biomimetic drug delivery system had no obvious hepatotoxicity and exhibited desirable biocompatibility. Conclusion: The present study provides a promising strategy for using exosome as nanocarrier to enhance the therapeutic effect of GCs against RA.

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Section: Discussionmentioning

confidence: 99%

Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis

et al. 2020

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“…As TRAP is the biomarkers for osteoclasts that reflect the bone resorption in vivo 58 , 59 , to further confirm the relief of bone destruction by DZ(1:1)@ALN was owing to the synergistic inhibitory effect of osteoclasts activation, TRAP staining was performed in bone metastatic tibias. Consistent with the severity degree of osteolysis, PBS, CDDP+ZOL and DSP@ALN group showed a large amount of osteoclasts, the monotherapy ZOL@ALN and DZ(1:1)@PEG showed moderate osteoclasts, while DZ(1:1)@ALN showed significantly reduced TRAP positive osteoclasts, possibly due to the dual function of active targeting and drug combination therapy ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption

Huang

Xiao

Guan

et al. 2020

Acta Pharmaceutica Sinica B

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The “vicious cycle” established between tumor growth and osteolysis aggravates the process of breast cancer bone metastasis, leading to life-threatening skeletal-related events that severely reduce survival and quality of life. To effectively interrupt the “vicious cycle”, innovative therapeutic strategies that not only reduce osteolysis but also relieve tumor burden are urgently needed. Herein, a bone-seeking moiety, alendronate (ALN), functionalized coordination polymer nanoparticles (DZ@ALN) co-delivering cisplatin prodrug (DSP) and antiresorptive agent zoledronate (ZOL) via Zn 2+ crosslinking for combination therapy was reported. The versatile DZ@ALN with a diameter of about 40 nm can cross the fissure in the bone marrow sinus capillaries, and possesses an excellent bone-seeking ability both in vitro and in vivo . Additionally, DZ@ALN could synergistically inhibit the proliferation of cancer cells, suppress the formation of osteoclast-like cells and induce the apoptosis of osteoclasts in vitro . Importantly, it could preferentially accumulate in bone affected site, remarkably inhibit the proliferation of tumor cells, relieving bone pain, and significantly inhibit the activation of osteoclasts, protecting the bone from destruction in vivo , eventually leading to the breakdown of “vicious cycle” without inducing obvious systemic toxicity. This innovative nanoagent combines chemotherapy and osteolysis inhibition, exhibiting an inspiring strategy for effective treatment of bone metastasis.

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“…These effects correlated with signi cantly lower histopathology scores based on H&E staining, signi cantly less cartilage and articular bone destruction based on SO staining and Micro-CT. The less severe bone destruction may be an indirect results of the ability of FPC-Exo/Dex (a) to reduce secretion of IL-1β and TNF-α, since these factors may promote the formation of osteoclasts [43][44][45]; and (b) promote secretion of IL-10, which can inhibit osteoclast formation. The superior therapeutic effects of FPC-Exo/Dex over the other Dex formulations may relate to its better targeting and internalization.…”

Section: Discussionmentioning

confidence: 99%

Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis

Yan

Zhong

Wang

et al. 2020

Preprint

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Backgroud: Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration and serious adverse reactions during long-term administration. To achieve better treatment and reduce side effect, we here established a biomimetic exosome (Exo) encapsulating dexamethasone sodium phosphate (Dex) nanoparticle (Exo/Dex), whose surface was modified with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol) compound to attain FPC-Exo/Dex active targeting drug delivery system. Results The size of FPC-Exo/Dex was 128.43 ± 16.27 nm, with a polydispersity index (PDI) of 0.36 ± 0.05, and the Zeta potential was − 22.73 ± 0.91 mV. The encapsulation efficiency (EE) of the preparation was 10.26 ± 0.73%, with drug loading efficiency (DLE) of 18.81 ± 2.05%. In vitro study showed this system displayed enhanced endocytosis and excellent anti-inflammation effect against RAW264.7 cells by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokine. Further biodistribution study showed the fluorescence intensity of FPC-Exo/Dex was stronger than other Dex formulations in joints, suggesting its enhanced accumulation to inflammation sites. In vivo pharmacodynamic experiment displayed FPC-Exo/Dex could preserve the bone and cartilage of CIA mice better and significantly reduce inflamed joints. Next in vivo safety evaluation demonstrated this biomimetic drug delivery system had no obvious hepatotoxicity and exhibited desirable biocompatibility. Conclusion The present study provides a promising strategy for using exosome as nanocarrier to enhance the therapeutic effect of GCs against RA.

show abstract

Benzydamine inhibits osteoclast differentiation and bone resorption via down-regulation of interleukin-1 expression

Cited by 47 publications

References 46 publications

Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis

Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis

Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption

Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis

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