Development of a Novel Co-Amorphous Curcumin and L-Arginine (1:2): Structural Characterization, Biological Activity and Pharmacokinetics
<b>Background:</b> Curcumin appears to be well tolerated and effective for managing chronic inflammatory pain, but its poor oral bioavailability has been a hurdle in its use as a therapeutic agent. The current study was performed to characterize a novel co-amorphous compound based on cur...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/17/1/11 |
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| Summary: | <b>Background:</b> Curcumin appears to be well tolerated and effective for managing chronic inflammatory pain, but its poor oral bioavailability has been a hurdle in its use as a therapeutic agent. The current study was performed to characterize a novel co-amorphous compound based on curcumin/L-arginine 1:2 (CAC12). <b>Methods</b>: Stability, solubility and structural characterization of the CAC12 were carried out by spectrometry techniques and in vitro assays, whereas the antinociceptive and anti-inflammatory effects were evaluated by CFA or carrageenan models. The mechanism of action was determined by cytokine quantification, and pharmacokinetic parameters were obtained through UPLC-MS/MS. The co-amorphous compound was prepared by fast solvent evaporation. Powder XRD, <sup>13</sup>C-NMR, ATR-FTIR and TGA/DSC thermal analysis showed a 1:2 stoichiometry for the CAC12. <b>Results</b>: CAC12 was 1000 times more soluble than curcumin, and it was stable for 1 month at 40 °C and 75% relative humidity or for 60 min in physiological medium at pH 4.5–6.8. Co-amorphous curcumin/L-arginine, but not curcumin + L-arginine, decreased carrageenan- or CFA-induced inflammation and nociception by decreasing IL-1α, IL-1β, IL-6, TNF-α, MCP-1 and CXCL1 cytokines. The bioavailability of free plasmatic curcumin increased about 22.4 times when it was given as CAC12 relative to a phytosome formulation at the equivalent dose. <b>Conclusions</b>: Results suggest the possible use of CAC12 to treat inflammatory pain disorders in human beings. |
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| ISSN: | 1999-4923 |