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The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats

BACKGROUND: Rheumatoid arthritis (RA), induced by the prolonged inappropriate inflammatory responses, is one of the most prevalent of all chronic inflammatory joint diseases. Curcumin (CM), a yellow hydrophobic polyphenol derived from the herb turmeric, has various pharmacological activities against...

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Autores principales: Zheng, Zhaoling, Sun, YanHua, Liu, Ziliang, Zhang, Mingqin, Li, Chunqing, Cai, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555965/
https://www.ncbi.nlm.nih.gov/pubmed/26345159
http://dx.doi.org/10.2147/DDDT.S90147
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author Zheng, Zhaoling
Sun, YanHua
Liu, Ziliang
Zhang, Mingqin
Li, Chunqing
Cai, Hui
author_facet Zheng, Zhaoling
Sun, YanHua
Liu, Ziliang
Zhang, Mingqin
Li, Chunqing
Cai, Hui
author_sort Zheng, Zhaoling
collection PubMed
description BACKGROUND: Rheumatoid arthritis (RA), induced by the prolonged inappropriate inflammatory responses, is one of the most prevalent of all chronic inflammatory joint diseases. Curcumin (CM), a yellow hydrophobic polyphenol derived from the herb turmeric, has various pharmacological activities against many chronic diseases and acts by inhibiting cell proliferation and metastasis and downregulating various factors, including nuclear factor kappa B, interleukin-1β and TNF-α. Given the pathogenesis of RA, we hypothesized that the drug also has antiarthritic effects. The aims of the present study included the following: 1) examining the therapeutic effect of CM administered via intravenous (iv) injection on RA and 2) formulating the drug into oil–water nanoemulsions (Ns) to overcome the low oral bioavailability of CM and achieve oral delivery of the drug. METHODS: The effect of CM administered through iv injection on adjuvant-induced arthritis in rats was studied in terms of paw swelling, weight indices of the thymus and spleen, and pathological changes in nuclear factor kappa B expression and inflammatory cytokines. Methotrexate was used as a positive control. The CM-Ns were prepared using a high-pressure homogenizing method and characterized with respect to the particle size and morphology. The stability of the CM-Ns in simulated gastrointestinal (GI) fluids and in vitro release were also investigated. A pharmacokinetic study of the CM-Ns and suspensions in which the plasma levels were determined using an high performance liquid chromatography method and the pharmacokinetic parameters were calculated based on a statistical moment theory was also performed in rats. RESULTS: CM administered via iv injection had a therapeutic effect on RA similar to methotrexate. CM-Ns with a diameter of approximately 150 nm were successfully prepared, and the drug was well encapsulated into the Ns without degradation in simulated GI conditions. The area under the curve (AUC) and C(max) for the CM-Ns were more than threefold greater than those for the suspensions; moreover, similar decreases in the levels of TNF-α and interleukin-1β in both synovial fluid and blood serum were obtained from oral administration of CM-Ns and iv injection. CONCLUSION: CM was an effective antiarthritic agent, and the present N formulation appeared to be a promising system that allowed RA therapy with CM to be converted from iv to oral administration.
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spelling pubmed-45559652015-09-04 The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats Zheng, Zhaoling Sun, YanHua Liu, Ziliang Zhang, Mingqin Li, Chunqing Cai, Hui Drug Des Devel Ther Original Research BACKGROUND: Rheumatoid arthritis (RA), induced by the prolonged inappropriate inflammatory responses, is one of the most prevalent of all chronic inflammatory joint diseases. Curcumin (CM), a yellow hydrophobic polyphenol derived from the herb turmeric, has various pharmacological activities against many chronic diseases and acts by inhibiting cell proliferation and metastasis and downregulating various factors, including nuclear factor kappa B, interleukin-1β and TNF-α. Given the pathogenesis of RA, we hypothesized that the drug also has antiarthritic effects. The aims of the present study included the following: 1) examining the therapeutic effect of CM administered via intravenous (iv) injection on RA and 2) formulating the drug into oil–water nanoemulsions (Ns) to overcome the low oral bioavailability of CM and achieve oral delivery of the drug. METHODS: The effect of CM administered through iv injection on adjuvant-induced arthritis in rats was studied in terms of paw swelling, weight indices of the thymus and spleen, and pathological changes in nuclear factor kappa B expression and inflammatory cytokines. Methotrexate was used as a positive control. The CM-Ns were prepared using a high-pressure homogenizing method and characterized with respect to the particle size and morphology. The stability of the CM-Ns in simulated gastrointestinal (GI) fluids and in vitro release were also investigated. A pharmacokinetic study of the CM-Ns and suspensions in which the plasma levels were determined using an high performance liquid chromatography method and the pharmacokinetic parameters were calculated based on a statistical moment theory was also performed in rats. RESULTS: CM administered via iv injection had a therapeutic effect on RA similar to methotrexate. CM-Ns with a diameter of approximately 150 nm were successfully prepared, and the drug was well encapsulated into the Ns without degradation in simulated GI conditions. The area under the curve (AUC) and C(max) for the CM-Ns were more than threefold greater than those for the suspensions; moreover, similar decreases in the levels of TNF-α and interleukin-1β in both synovial fluid and blood serum were obtained from oral administration of CM-Ns and iv injection. CONCLUSION: CM was an effective antiarthritic agent, and the present N formulation appeared to be a promising system that allowed RA therapy with CM to be converted from iv to oral administration. Dove Medical Press 2015-08-27 /pmc/articles/PMC4555965/ /pubmed/26345159 http://dx.doi.org/10.2147/DDDT.S90147 Text en © 2015 Zheng et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Zheng, Zhaoling
Sun, YanHua
Liu, Ziliang
Zhang, Mingqin
Li, Chunqing
Cai, Hui
The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats
title The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats
title_full The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats
title_fullStr The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats
title_full_unstemmed The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats
title_short The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats
title_sort effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555965/
https://www.ncbi.nlm.nih.gov/pubmed/26345159
http://dx.doi.org/10.2147/DDDT.S90147
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