Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer Treatment
Breast cancer is the second most common cancer in women worldwide. Long-term treatment with conventional chemotherapy may result in severe systemic side effects. Therefore, the localized delivery of chemotherapy helps to overcome such a problem. In this article, self-assembling hydrogels were constr...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Online Access: | https://www.mdpi.com/2310-2861/9/4/326 |
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| author | Saud Almawash Ahmed M. Mohammed Mohamed A. El Hamd Shaaban K. Osman |
| author_facet | Saud Almawash Ahmed M. Mohammed Mohamed A. El Hamd Shaaban K. Osman |
| author_sort | Saud Almawash |
| collection | DOAJ |
| description | Breast cancer is the second most common cancer in women worldwide. Long-term treatment with conventional chemotherapy may result in severe systemic side effects. Therefore, the localized delivery of chemotherapy helps to overcome such a problem. In this article, self-assembling hydrogels were constructed via inclusion complexation between host β-cyclodextrin polymers (8armPEG20k-CD and pβ-CD) and the guest polymers 8-armed poly(ethylene glycol) capped either with cholesterol (8armPEG20k-chol) or adamantane (8armPEG20k-Ad) and were loaded with 5-fluorouracil (5-FU) and methotrexate (MTX). The prepared hydrogels were characterized by SEM and rheological behaviors. The in vitro release of 5-FU and MTX was studied. The cytotoxicity of our modified systems was investigated against breast tumor cells (MCF-7) using an MTT assay. Additionally, the histopathological changes in breast tissues were monitored before and after their intratumor injection. The results of rheological characterization indicated the viscoelastic behavior in all cases except for 8armPEG-Ad. In vitro release results showed a variable range of release profiles from 6 to 21 days, depending on the hydrogel composition. MTT findings indicated the inhibition ability of our systems against the viability of cancer cells depending on the kind and concentration of the hydrogel and the incubation period. Moreover, the results of histopathology showed the improvement of cancer manifestation (swelling and inflammation) after intratumor injection of loaded hydrogel systems. In conclusion, the obtained results indicated the applicability of the modified hydrogels as injectable vehicles for both loading and controlled release of anticancer therapies. |
| first_indexed | 2024-03-11T05:00:22Z |
| format | Article |
| id | doaj.art-addbc196bc6e4008a450233f910206bd |
| institution | Directory Open Access Journal |
| issn | 2310-2861 |
| language | English |
| last_indexed | 2024-03-11T05:00:22Z |
| publishDate | 2023-04-01 |
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| spelling | doaj.art-addbc196bc6e4008a450233f910206bd2023-11-17T19:21:52ZengMDPI AGGels2310-28612023-04-019432610.3390/gels9040326Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer TreatmentSaud Almawash0Ahmed M. Mohammed1Mohamed A. El Hamd2Shaaban K. Osman3Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqraa 11961, Saudi ArabiaDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, EgyptDepartment of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqraa 11961, Saudi ArabiaDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, EgyptBreast cancer is the second most common cancer in women worldwide. Long-term treatment with conventional chemotherapy may result in severe systemic side effects. Therefore, the localized delivery of chemotherapy helps to overcome such a problem. In this article, self-assembling hydrogels were constructed via inclusion complexation between host β-cyclodextrin polymers (8armPEG20k-CD and pβ-CD) and the guest polymers 8-armed poly(ethylene glycol) capped either with cholesterol (8armPEG20k-chol) or adamantane (8armPEG20k-Ad) and were loaded with 5-fluorouracil (5-FU) and methotrexate (MTX). The prepared hydrogels were characterized by SEM and rheological behaviors. The in vitro release of 5-FU and MTX was studied. The cytotoxicity of our modified systems was investigated against breast tumor cells (MCF-7) using an MTT assay. Additionally, the histopathological changes in breast tissues were monitored before and after their intratumor injection. The results of rheological characterization indicated the viscoelastic behavior in all cases except for 8armPEG-Ad. In vitro release results showed a variable range of release profiles from 6 to 21 days, depending on the hydrogel composition. MTT findings indicated the inhibition ability of our systems against the viability of cancer cells depending on the kind and concentration of the hydrogel and the incubation period. Moreover, the results of histopathology showed the improvement of cancer manifestation (swelling and inflammation) after intratumor injection of loaded hydrogel systems. In conclusion, the obtained results indicated the applicability of the modified hydrogels as injectable vehicles for both loading and controlled release of anticancer therapies.https://www.mdpi.com/2310-2861/9/4/326β-cyclodextrin polymers5-fluorouracilmethotrexatecholesterolpolyethylene glycolinjectable hydrogels |
| spellingShingle | Saud Almawash Ahmed M. Mohammed Mohamed A. El Hamd Shaaban K. Osman Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer Treatment Gels β-cyclodextrin polymers 5-fluorouracil methotrexate cholesterol polyethylene glycol injectable hydrogels |
| title | Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer Treatment |
| title_full | Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer Treatment |
| title_fullStr | Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer Treatment |
| title_full_unstemmed | Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer Treatment |
| title_short | Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer Treatment |
| title_sort | injectable hydrogels based on cyclodextrin cholesterol inclusion complexation and loaded with 5 fluorouracil methotrexate for breast cancer treatment |
| topic | β-cyclodextrin polymers 5-fluorouracil methotrexate cholesterol polyethylene glycol injectable hydrogels |
| url | https://www.mdpi.com/2310-2861/9/4/326 |
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