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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2024-12-01
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| author | Jose Antonio Mancillas-Quiroz Miriam del Carmen Carrasco-Portugal Karina Mondragón-Vásquez Juan Carlos Huerta-Cruz Juan Rodríguez-Silverio Leyanis Rodríguez-Vera Juan Gerardo Reyes-García Francisco Javier Flores-Murrieta Jorge Guillermo Domínguez-Chávez Héctor Isaac Rocha-González |
| author_facet | Jose Antonio Mancillas-Quiroz Miriam del Carmen Carrasco-Portugal Karina Mondragón-Vásquez Juan Carlos Huerta-Cruz Juan Rodríguez-Silverio Leyanis Rodríguez-Vera Juan Gerardo Reyes-García Francisco Javier Flores-Murrieta Jorge Guillermo Domínguez-Chávez Héctor Isaac Rocha-González |
| author_sort | Jose Antonio Mancillas-Quiroz |
| collection | DOAJ |
| description | <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. |
| format | Article |
| id | doaj-art-838c51319398491d8298abfcd8a126b0 |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-12-01 |
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| series | Pharmaceutics |
| spelling | doaj-art-838c51319398491d8298abfcd8a126b02025-01-24T13:45:34ZengMDPI AGPharmaceutics1999-49232024-12-011711110.3390/pharmaceutics17010011Development of a Novel Co-Amorphous Curcumin and L-Arginine (1:2): Structural Characterization, Biological Activity and PharmacokineticsJose Antonio Mancillas-Quiroz0Miriam del Carmen Carrasco-Portugal1Karina Mondragón-Vásquez2Juan Carlos Huerta-Cruz3Juan Rodríguez-Silverio4Leyanis Rodríguez-Vera5Juan Gerardo Reyes-García6Francisco Javier Flores-Murrieta7Jorge Guillermo Domínguez-Chávez8Héctor Isaac Rocha-González9Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoInstituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, Ciudad de México 14080, MexicoFacultad de Bioanálisis Veracruz, Universidad Veracruzana, Veracruz 91700, MexicoInstituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, Ciudad de México 14080, MexicoEscuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoCTI Clinical Trial & Consulting Clinical Research Center, Norwood, OH 45212, USAEscuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoEscuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoFacultad de Bioanálisis Veracruz, Universidad Veracruzana, Veracruz 91700, MexicoEscuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico<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.https://www.mdpi.com/1999-4923/17/1/11bioavailabilityco-amorphouscurcumincytokinesinflammationL-arginine |
| spellingShingle | Jose Antonio Mancillas-Quiroz Miriam del Carmen Carrasco-Portugal Karina Mondragón-Vásquez Juan Carlos Huerta-Cruz Juan Rodríguez-Silverio Leyanis Rodríguez-Vera Juan Gerardo Reyes-García Francisco Javier Flores-Murrieta Jorge Guillermo Domínguez-Chávez Héctor Isaac Rocha-González Development of a Novel Co-Amorphous Curcumin and L-Arginine (1:2): Structural Characterization, Biological Activity and Pharmacokinetics Pharmaceutics bioavailability co-amorphous curcumin cytokines inflammation L-arginine |
| title | Development of a Novel Co-Amorphous Curcumin and L-Arginine (1:2): Structural Characterization, Biological Activity and Pharmacokinetics |
| title_full | Development of a Novel Co-Amorphous Curcumin and L-Arginine (1:2): Structural Characterization, Biological Activity and Pharmacokinetics |
| title_fullStr | Development of a Novel Co-Amorphous Curcumin and L-Arginine (1:2): Structural Characterization, Biological Activity and Pharmacokinetics |
| title_full_unstemmed | Development of a Novel Co-Amorphous Curcumin and L-Arginine (1:2): Structural Characterization, Biological Activity and Pharmacokinetics |
| title_short | Development of a Novel Co-Amorphous Curcumin and L-Arginine (1:2): Structural Characterization, Biological Activity and Pharmacokinetics |
| title_sort | development of a novel co amorphous curcumin and l arginine 1 2 structural characterization biological activity and pharmacokinetics |
| topic | bioavailability co-amorphous curcumin cytokines inflammation L-arginine |
| url | https://www.mdpi.com/1999-4923/17/1/11 |
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