Styrene maleic acid encapsulated raloxifene micelles for management of inflammatory bowel disease
Abstract Background Inflammatory bowel disease (IBD) comprises a group of disorders that manifest through chronic inflammation of the colon and small intestine. Although the exact cause of IBD is still unclear, dysfunctional immunoregulation involving overproduction of inflammatory cytokines such as...
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Wiley
2017-08-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s40169-017-0157-2 |
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| author | Khaled Greish Safa Taha Anfal Jasim Sara Abd Elghany Ameera Sultan Ali AlKhateeb Manal Othman Fang Jun Sebastien Taurin Moiz Bakhiet |
| author_facet | Khaled Greish Safa Taha Anfal Jasim Sara Abd Elghany Ameera Sultan Ali AlKhateeb Manal Othman Fang Jun Sebastien Taurin Moiz Bakhiet |
| author_sort | Khaled Greish |
| collection | DOAJ |
| description | Abstract Background Inflammatory bowel disease (IBD) comprises a group of disorders that manifest through chronic inflammation of the colon and small intestine. Although the exact cause of IBD is still unclear, dysfunctional immunoregulation involving overproduction of inflammatory cytokines such as TNF-α, and IL-6 have been implicated in pathogenesis. Current therapy relies on immunosuppression, cytotoxic drugs, and monoclonal antibodies against TNF-α. These classes of drugs have severe side-effects, especially when used for long duration. Our previous work with raloxifene, a selective estrogen receptor modulator, has shown that the drug, and to a greater extent its micellar formulation, has a significant suppressive effect on NF-κB, an essential immune-regulator. This finding directed the current work towards testing the anti-inflammatory and immunomodulatory effects of raloxifene using cell lines, as well as testing the potential use of the styrene maleic acid (SMA) micelles loaded with raloxifene (SMA-Ral) against dextran sulfate sodium (DSS) induced colitis in an in vivo model of IBD. Results Treatment of MCF-7 cells with TNF-α was shown to protect the cells from the cytotoxic effect of raloxifene (42 vs. 10% cell death, with TNF-α. Treating CaCo-2 cells with both free and SMA-Ral improved cell survival after exposure to 2% DDS with significantly higher protection with SMA-Ral. Treatment of U-937 with SMA-Ral and free-Ral resulted in down-regulation of TNF-α, IL-1β, IL-6, and MIP1α, with greater inhibition of the SMA-Ral, compared to free Ral. Balb/c mice treated with raloxifene and SMA-Ral showed weight gain at 14 days, compared to the control group (122, and 115% respectively). Treatment with raloxifene prevented DSS-induced diarrhea in 6/6 of free raloxifene treated mice and in 5/6 mice treated with SMA-Ral. Control group of DSS-treated mice showed average colon length of 7.4 cm compared to 13 cm in the control group. The average colon length was 12.3 and 11.5 cm for raloxifene and SMA-Ral treated groups, respectively. Furthermore, inflammatory cytokines such as IL-6 and TNF-α were reduced in serum of animals treated with free-Ral and SMA-Ral. Conclusions Raloxifene and its micellar formulation warrants further studies to understand their effect on the treatment of colitis. Graphical abstract SMA-Raloxifene preparation and its in vivo and in vitro effect on colitis |
| first_indexed | 2024-12-11T05:44:52Z |
| format | Article |
| id | doaj.art-4c77ea9fd113485396e58e1eaaf2095c |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-12-11T05:44:52Z |
| publishDate | 2017-08-01 |
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| series | Clinical and Translational Medicine |
| spelling | doaj.art-4c77ea9fd113485396e58e1eaaf2095c2022-12-22T01:19:00ZengWileyClinical and Translational Medicine2001-13262017-08-016111010.1186/s40169-017-0157-2Styrene maleic acid encapsulated raloxifene micelles for management of inflammatory bowel diseaseKhaled Greish0Safa Taha1Anfal Jasim2Sara Abd Elghany3Ameera Sultan4Ali AlKhateeb5Manal Othman6Fang Jun7Sebastien Taurin8Moiz Bakhiet9Department of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf UniversityDepartment of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf UniversityDepartment of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf UniversityDepartment of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf UniversityDepartment of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf UniversityDepartment of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf UniversityDepartment of Anatomy, College of Medicine and Medical Sciences, Arabian Gulf UniversityDepartment of Pharmacology and Oncology, Sojo UniversityDepartment of Obstetrics and Gynecology, University of UtahDepartment of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf UniversityAbstract Background Inflammatory bowel disease (IBD) comprises a group of disorders that manifest through chronic inflammation of the colon and small intestine. Although the exact cause of IBD is still unclear, dysfunctional immunoregulation involving overproduction of inflammatory cytokines such as TNF-α, and IL-6 have been implicated in pathogenesis. Current therapy relies on immunosuppression, cytotoxic drugs, and monoclonal antibodies against TNF-α. These classes of drugs have severe side-effects, especially when used for long duration. Our previous work with raloxifene, a selective estrogen receptor modulator, has shown that the drug, and to a greater extent its micellar formulation, has a significant suppressive effect on NF-κB, an essential immune-regulator. This finding directed the current work towards testing the anti-inflammatory and immunomodulatory effects of raloxifene using cell lines, as well as testing the potential use of the styrene maleic acid (SMA) micelles loaded with raloxifene (SMA-Ral) against dextran sulfate sodium (DSS) induced colitis in an in vivo model of IBD. Results Treatment of MCF-7 cells with TNF-α was shown to protect the cells from the cytotoxic effect of raloxifene (42 vs. 10% cell death, with TNF-α. Treating CaCo-2 cells with both free and SMA-Ral improved cell survival after exposure to 2% DDS with significantly higher protection with SMA-Ral. Treatment of U-937 with SMA-Ral and free-Ral resulted in down-regulation of TNF-α, IL-1β, IL-6, and MIP1α, with greater inhibition of the SMA-Ral, compared to free Ral. Balb/c mice treated with raloxifene and SMA-Ral showed weight gain at 14 days, compared to the control group (122, and 115% respectively). Treatment with raloxifene prevented DSS-induced diarrhea in 6/6 of free raloxifene treated mice and in 5/6 mice treated with SMA-Ral. Control group of DSS-treated mice showed average colon length of 7.4 cm compared to 13 cm in the control group. The average colon length was 12.3 and 11.5 cm for raloxifene and SMA-Ral treated groups, respectively. Furthermore, inflammatory cytokines such as IL-6 and TNF-α were reduced in serum of animals treated with free-Ral and SMA-Ral. Conclusions Raloxifene and its micellar formulation warrants further studies to understand their effect on the treatment of colitis. Graphical abstract SMA-Raloxifene preparation and its in vivo and in vitro effect on colitishttp://link.springer.com/article/10.1186/s40169-017-0157-2Styrene maleic acid (SMA)RaloxifeneInflammatory bowel disease (IBD)NanomedicineEnhanced permeability and retention effect (EPR)Inflammatory cytokines |
| spellingShingle | Khaled Greish Safa Taha Anfal Jasim Sara Abd Elghany Ameera Sultan Ali AlKhateeb Manal Othman Fang Jun Sebastien Taurin Moiz Bakhiet Styrene maleic acid encapsulated raloxifene micelles for management of inflammatory bowel disease Clinical and Translational Medicine Styrene maleic acid (SMA) Raloxifene Inflammatory bowel disease (IBD) Nanomedicine Enhanced permeability and retention effect (EPR) Inflammatory cytokines |
| title | Styrene maleic acid encapsulated raloxifene micelles for management of inflammatory bowel disease |
| title_full | Styrene maleic acid encapsulated raloxifene micelles for management of inflammatory bowel disease |
| title_fullStr | Styrene maleic acid encapsulated raloxifene micelles for management of inflammatory bowel disease |
| title_full_unstemmed | Styrene maleic acid encapsulated raloxifene micelles for management of inflammatory bowel disease |
| title_short | Styrene maleic acid encapsulated raloxifene micelles for management of inflammatory bowel disease |
| title_sort | styrene maleic acid encapsulated raloxifene micelles for management of inflammatory bowel disease |
| topic | Styrene maleic acid (SMA) Raloxifene Inflammatory bowel disease (IBD) Nanomedicine Enhanced permeability and retention effect (EPR) Inflammatory cytokines |
| url | http://link.springer.com/article/10.1186/s40169-017-0157-2 |
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