Enhancing the Bioavailability and Efficacy of Vismodegib for the Control of Skin Cancer: In Vitro and In Vivo Studies
Skin cancer is the most frequent cancer throughout the world. Vismodegib (VSD) is a hedgehog blocker approved for the prevention and treatment of skin cancer. VSD, however, is poorly bioavailable and has been linked to side effects. This work focused on designing a nano-invasome gel as a vehicle for...
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MDPI AG
2022-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/2/126 |
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| author | Heba F. Salem Amr Gamal Haitham Saeed Marwa Kamal Alaa S. Tulbah |
| author_facet | Heba F. Salem Amr Gamal Haitham Saeed Marwa Kamal Alaa S. Tulbah |
| author_sort | Heba F. Salem |
| collection | DOAJ |
| description | Skin cancer is the most frequent cancer throughout the world. Vismodegib (VSD) is a hedgehog blocker approved for the prevention and treatment of skin cancer. VSD, however, is poorly bioavailable and has been linked to side effects. This work focused on designing a nano-invasome gel as a vehicle for enhancing the permeation, bioavailability, and efficacy of VSD. Additionally, the combined effect of terpenes and ethanol was studied on the permeation of VSD compared with liposomes. The prepared VSD-loaded invasomes (VLI) formulation included cineole (1%<i>v/v</i>), cholesterol (0.15%<i>w/w</i>), phospholipid (2%<i>w/w</i>), and ethanol (3%<i>v/v</i>) and displayed an entrapment efficiency of 87.73 ± 3.82%, a vesicle size of 188.27 ± 3.25 nm, and a steady-state flux of 9.83 ± 0.11 µg/cm<sup>2</sup>/h. The VLI formulation was vigorously stirred into a carbopol base before being characterized in vivo to investigate the permeation, bioavailability, and efficacy of VSD. The VLI gel enhanced the dermal permeation of VSD and, as a result, had 3.59 times higher bioavailability with excellent antitumor action as compared to oral VSD. In summary, as an alternative to oral administration for skin cancer treatment, invasomes are efficient carriers for delivering VSD and enhancing its transdermal flux into deep skin layers. |
| first_indexed | 2024-03-09T21:16:15Z |
| format | Article |
| id | doaj.art-c3e6e9faea6542f6833fc73a04ab6f83 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T21:16:15Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-c3e6e9faea6542f6833fc73a04ab6f832023-11-23T21:33:25ZengMDPI AGPharmaceuticals1424-82472022-01-0115212610.3390/ph15020126Enhancing the Bioavailability and Efficacy of Vismodegib for the Control of Skin Cancer: In Vitro and In Vivo StudiesHeba F. Salem0Amr Gamal1Haitham Saeed2Marwa Kamal3Alaa S. Tulbah4Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 625617, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 625617, EgyptClinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 625617, EgyptClinical Pharmacy Department, Faculty of Pharmacy, Fayoum University, Fayoum 63514, EgyptDepartment of Pharmaceutics, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi ArabiaSkin cancer is the most frequent cancer throughout the world. Vismodegib (VSD) is a hedgehog blocker approved for the prevention and treatment of skin cancer. VSD, however, is poorly bioavailable and has been linked to side effects. This work focused on designing a nano-invasome gel as a vehicle for enhancing the permeation, bioavailability, and efficacy of VSD. Additionally, the combined effect of terpenes and ethanol was studied on the permeation of VSD compared with liposomes. The prepared VSD-loaded invasomes (VLI) formulation included cineole (1%<i>v/v</i>), cholesterol (0.15%<i>w/w</i>), phospholipid (2%<i>w/w</i>), and ethanol (3%<i>v/v</i>) and displayed an entrapment efficiency of 87.73 ± 3.82%, a vesicle size of 188.27 ± 3.25 nm, and a steady-state flux of 9.83 ± 0.11 µg/cm<sup>2</sup>/h. The VLI formulation was vigorously stirred into a carbopol base before being characterized in vivo to investigate the permeation, bioavailability, and efficacy of VSD. The VLI gel enhanced the dermal permeation of VSD and, as a result, had 3.59 times higher bioavailability with excellent antitumor action as compared to oral VSD. In summary, as an alternative to oral administration for skin cancer treatment, invasomes are efficient carriers for delivering VSD and enhancing its transdermal flux into deep skin layers.https://www.mdpi.com/1424-8247/15/2/126skin cancervismodegibinvasomesterpenesbioavailability |
| spellingShingle | Heba F. Salem Amr Gamal Haitham Saeed Marwa Kamal Alaa S. Tulbah Enhancing the Bioavailability and Efficacy of Vismodegib for the Control of Skin Cancer: In Vitro and In Vivo Studies Pharmaceuticals skin cancer vismodegib invasomes terpenes bioavailability |
| title | Enhancing the Bioavailability and Efficacy of Vismodegib for the Control of Skin Cancer: In Vitro and In Vivo Studies |
| title_full | Enhancing the Bioavailability and Efficacy of Vismodegib for the Control of Skin Cancer: In Vitro and In Vivo Studies |
| title_fullStr | Enhancing the Bioavailability and Efficacy of Vismodegib for the Control of Skin Cancer: In Vitro and In Vivo Studies |
| title_full_unstemmed | Enhancing the Bioavailability and Efficacy of Vismodegib for the Control of Skin Cancer: In Vitro and In Vivo Studies |
| title_short | Enhancing the Bioavailability and Efficacy of Vismodegib for the Control of Skin Cancer: In Vitro and In Vivo Studies |
| title_sort | enhancing the bioavailability and efficacy of vismodegib for the control of skin cancer in vitro and in vivo studies |
| topic | skin cancer vismodegib invasomes terpenes bioavailability |
| url | https://www.mdpi.com/1424-8247/15/2/126 |
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