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

Zheng Z, Sun Y, Liu Z, Zhang M, Li C, Cai H - Drug Des Devel Ther (2015)

Bottom Line: 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 Cmax 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Traditional Chinese Medicine, Dongying People's Hospital, Dongying, People's Republic of China.

ABSTRACT

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 Cmax 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.

No MeSH data available.


Related in: MedlinePlus

Therapeutic effects of CM formulations on inflammatory cytokines in (A) synovial fluid and (B) blood serum after oral administration of CM suspensions or Ns or iv injection of a CM solution every day for 15 days, with saline as control.Note: **P<0.01.Abbreviations: CM, curcumin; Ns, nanoemulsions; iv, intravenous; IL-1β, interleukin-1β; MTX, methotrexate G; TNF-α, tumor necrosis factor α.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4555965&req=5

f8-dddt-9-4931: Therapeutic effects of CM formulations on inflammatory cytokines in (A) synovial fluid and (B) blood serum after oral administration of CM suspensions or Ns or iv injection of a CM solution every day for 15 days, with saline as control.Note: **P<0.01.Abbreviations: CM, curcumin; Ns, nanoemulsions; iv, intravenous; IL-1β, interleukin-1β; MTX, methotrexate G; TNF-α, tumor necrosis factor α.

Mentions: Following the oral administration of the two CM formulations (CM-Ns and suspensions) and the iv injection of the CM solution, the expression of the two most important cytokines, TNF-α and IL-1β, was examined. The therapeutic effect of the CM formulations on AIA is displayed in Figure 8. Compared with the saline group, the CM injection resulted in a significant reduction in the levels of TNF-α and IL-1β in both synovial fluid and blood serum, which the reduction was similar to that MTX group. These results confirmed the better effect of CM on AIA. After the oral administration of the CM-Ns or suspensions, as expected, the levels of the two indicators in the synovial fluid of the CM-Ns-treated group were more than twofold lower than those of the suspension group (Figure 8A). A similar threefold decrease was observed in the blood serum (Figure 8B). These results indicate the better therapeutic effect of CM-Ns than CM suspensions on RA. Importantly, the levels of the two indicators from the animals that were orally administered the CM-Ns and those injected with the CM solution were similar, suggesting the feasibility of oral administration of CM-Ns for RA therapy.


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

Zheng Z, Sun Y, Liu Z, Zhang M, Li C, Cai H - Drug Des Devel Ther (2015)

Therapeutic effects of CM formulations on inflammatory cytokines in (A) synovial fluid and (B) blood serum after oral administration of CM suspensions or Ns or iv injection of a CM solution every day for 15 days, with saline as control.Note: **P<0.01.Abbreviations: CM, curcumin; Ns, nanoemulsions; iv, intravenous; IL-1β, interleukin-1β; MTX, methotrexate G; TNF-α, tumor necrosis factor α.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555965&req=5

f8-dddt-9-4931: Therapeutic effects of CM formulations on inflammatory cytokines in (A) synovial fluid and (B) blood serum after oral administration of CM suspensions or Ns or iv injection of a CM solution every day for 15 days, with saline as control.Note: **P<0.01.Abbreviations: CM, curcumin; Ns, nanoemulsions; iv, intravenous; IL-1β, interleukin-1β; MTX, methotrexate G; TNF-α, tumor necrosis factor α.
Mentions: Following the oral administration of the two CM formulations (CM-Ns and suspensions) and the iv injection of the CM solution, the expression of the two most important cytokines, TNF-α and IL-1β, was examined. The therapeutic effect of the CM formulations on AIA is displayed in Figure 8. Compared with the saline group, the CM injection resulted in a significant reduction in the levels of TNF-α and IL-1β in both synovial fluid and blood serum, which the reduction was similar to that MTX group. These results confirmed the better effect of CM on AIA. After the oral administration of the CM-Ns or suspensions, as expected, the levels of the two indicators in the synovial fluid of the CM-Ns-treated group were more than twofold lower than those of the suspension group (Figure 8A). A similar threefold decrease was observed in the blood serum (Figure 8B). These results indicate the better therapeutic effect of CM-Ns than CM suspensions on RA. Importantly, the levels of the two indicators from the animals that were orally administered the CM-Ns and those injected with the CM solution were similar, suggesting the feasibility of oral administration of CM-Ns for RA therapy.

Bottom Line: 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 Cmax 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Traditional Chinese Medicine, Dongying People's Hospital, Dongying, People's Republic of China.

ABSTRACT

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 Cmax 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.

No MeSH data available.


Related in: MedlinePlus