In situ forming gels as subcutaneous delivery systems of curcumin and piperine
Abstract In this study an in situ forming gel for curcumin and piperine delivery is investigated as a long-lasting strategy in the local treatment of inflammatory and degenerative joint disease, such as osteoarthritis and rheumatoid arthritis. Particularly glyceryl monooleate, in association with ph...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-87750-w |
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| author | Walter Pula Alessia Pepe Francesca Ferrara Agnese Bondi Paolo Mariani Maria Grazia Ortore Alessandra Pecorelli John Ivarsson Giuseppe Valacchi Elisabetta Esposito |
| author_facet | Walter Pula Alessia Pepe Francesca Ferrara Agnese Bondi Paolo Mariani Maria Grazia Ortore Alessandra Pecorelli John Ivarsson Giuseppe Valacchi Elisabetta Esposito |
| author_sort | Walter Pula |
| collection | DOAJ |
| description | Abstract In this study an in situ forming gel for curcumin and piperine delivery is investigated as a long-lasting strategy in the local treatment of inflammatory and degenerative joint disease, such as osteoarthritis and rheumatoid arthritis. Particularly glyceryl monooleate, in association with phosphatidylcholine and ethanol, were employed. Different ratios between excipients were tested, with the aim to obtain a liquid form suitable for subcutaneous injection, gaining a semisolid consistency in contact with biological fluids. A formulative study was conducted to assess the composition impact on the structural properties of the formulations, particularly focusing on injectability and phase transition. Curcumin and piperine were loaded, singularly or jointly, in selected in situ forming gels. Structural characterization, performed by X-ray scattering, revealed disordered reverse micellar phases, undergoing transition to hexagonal and cubic Pn3m phase upon hydration. In vitro dialysis release study demonstrated a sustained release of both drugs over 96 h, with a faster release in the case of jointly loaded drugs. Mechanistic analysis and water uptake studies indicated a drug release governed by both diffusion and swelling/erosion of the lipid supramolecular structure. Furthermore, an ex vivo release analysis performed using human skin explants suggested the formulation suitability for subcutaneous injection, indicating that the presence of piperine in the in situ formed gel allowed to double the curcumin release with respect to the simple curcumin loaded gel. |
| format | Article |
| id | doaj-art-de4834be68764d78b56f76a47cbf989f |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-de4834be68764d78b56f76a47cbf989f2025-01-26T12:27:02ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-87750-wIn situ forming gels as subcutaneous delivery systems of curcumin and piperineWalter Pula0Alessia Pepe1Francesca Ferrara2Agnese Bondi3Paolo Mariani4Maria Grazia Ortore5Alessandra Pecorelli6John Ivarsson7Giuseppe Valacchi8Elisabetta Esposito9Department of Chemical, Pharmaceutical and Agricultural Sciences, University of FerraraDepartment of Life and Environmental Sciences, Marche Polytechnic UniversityDepartment of Chemical, Pharmaceutical and Agricultural Sciences, University of FerraraDepartment of Chemical, Pharmaceutical and Agricultural Sciences, University of FerraraDepartment of Life and Environmental Sciences, Marche Polytechnic UniversityDepartment of Life and Environmental Sciences, Marche Polytechnic UniversityDepartment of Environmental and Prevention Sciences, University of FerraraPlants for Human Health Institute, Animal Science Department, NC State UniversityDepartment of Environmental and Prevention Sciences, University of FerraraDepartment of Chemical, Pharmaceutical and Agricultural Sciences, University of FerraraAbstract In this study an in situ forming gel for curcumin and piperine delivery is investigated as a long-lasting strategy in the local treatment of inflammatory and degenerative joint disease, such as osteoarthritis and rheumatoid arthritis. Particularly glyceryl monooleate, in association with phosphatidylcholine and ethanol, were employed. Different ratios between excipients were tested, with the aim to obtain a liquid form suitable for subcutaneous injection, gaining a semisolid consistency in contact with biological fluids. A formulative study was conducted to assess the composition impact on the structural properties of the formulations, particularly focusing on injectability and phase transition. Curcumin and piperine were loaded, singularly or jointly, in selected in situ forming gels. Structural characterization, performed by X-ray scattering, revealed disordered reverse micellar phases, undergoing transition to hexagonal and cubic Pn3m phase upon hydration. In vitro dialysis release study demonstrated a sustained release of both drugs over 96 h, with a faster release in the case of jointly loaded drugs. Mechanistic analysis and water uptake studies indicated a drug release governed by both diffusion and swelling/erosion of the lipid supramolecular structure. Furthermore, an ex vivo release analysis performed using human skin explants suggested the formulation suitability for subcutaneous injection, indicating that the presence of piperine in the in situ formed gel allowed to double the curcumin release with respect to the simple curcumin loaded gel.https://doi.org/10.1038/s41598-025-87750-wGlyceryl MonooleateSkinHexagonal phaseCurcuminPiperine |
| spellingShingle | Walter Pula Alessia Pepe Francesca Ferrara Agnese Bondi Paolo Mariani Maria Grazia Ortore Alessandra Pecorelli John Ivarsson Giuseppe Valacchi Elisabetta Esposito In situ forming gels as subcutaneous delivery systems of curcumin and piperine Scientific Reports Glyceryl Monooleate Skin Hexagonal phase Curcumin Piperine |
| title | In situ forming gels as subcutaneous delivery systems of curcumin and piperine |
| title_full | In situ forming gels as subcutaneous delivery systems of curcumin and piperine |
| title_fullStr | In situ forming gels as subcutaneous delivery systems of curcumin and piperine |
| title_full_unstemmed | In situ forming gels as subcutaneous delivery systems of curcumin and piperine |
| title_short | In situ forming gels as subcutaneous delivery systems of curcumin and piperine |
| title_sort | in situ forming gels as subcutaneous delivery systems of curcumin and piperine |
| topic | Glyceryl Monooleate Skin Hexagonal phase Curcumin Piperine |
| url | https://doi.org/10.1038/s41598-025-87750-w |
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