Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in Mice
To achieve the best treatment of skin cancer, drug penetration inside the deepest layers of the skin is an important scientific interest. We designed an ethosome formulation that serves as a carrier for metformin and measured the in vitro skin permeation. We also aimed to measure the antitumor activ...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/6/657 |
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| author | Ibrahim A. Mousa Taha M. Hammady Shadeed Gad Sawsan A. Zaitone Mohamed El-Sherbiny Ossama M. Sayed |
| author_facet | Ibrahim A. Mousa Taha M. Hammady Shadeed Gad Sawsan A. Zaitone Mohamed El-Sherbiny Ossama M. Sayed |
| author_sort | Ibrahim A. Mousa |
| collection | DOAJ |
| description | To achieve the best treatment of skin cancer, drug penetration inside the deepest layers of the skin is an important scientific interest. We designed an ethosome formulation that serves as a carrier for metformin and measured the in vitro skin permeation. We also aimed to measure the antitumor activity of the optimal ethosomal preparation when applied topically to chemically induced skin cancer in mice. We utilized a statistical Box–Behnken experimental design and applied three variables at three levels: lecithin concentration, cholesterol concentration and a mixture of ethanol and isopropyl alcohol concentrations. All formulations were prepared to calculate the entrapment efficiency %, zeta potential, size of the vesicles and drug release % after 1, 2, 4, 8 and 24 h. The size of the vesicles for the formulations was between 124 ± 14.2 nm and 560 ± 127 nm, while the entrapment efficiency was between 97.8 ± 0.23% and 99.4 ± 0.24%, and the drug release % after 8 h was between 38 ± 0.82% and 66 ± 0.52%. All formulations were introduced into the Box–Behnken software, which selected three formulations; then, one was assigned as an optimal formula. The in vivo antitumor activity of metformin-loaded ethosomal gel on skin cancer was greater than the antitumor activity of the gel preparation containing free metformin. Lower lecithin, high ethanol and isopropyl alcohol and moderate cholesterol contents improved the permeation rate. Overall, we can conclude that metformin-loaded ethosomes are a promising remedy for treating skin cancers, and more studies are warranted to approve this activity in other animal models of skin cancers. |
| first_indexed | 2024-03-09T22:47:15Z |
| format | Article |
| id | doaj.art-461471d1d49247739bed4ecb09a48cd6 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:47:15Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-461471d1d49247739bed4ecb09a48cd62023-11-23T18:26:26ZengMDPI AGPharmaceuticals1424-82472022-05-0115665710.3390/ph15060657Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in MiceIbrahim A. Mousa0Taha M. Hammady1Shadeed Gad2Sawsan A. Zaitone3Mohamed El-Sherbiny4Ossama M. Sayed5General Authority of Health Care, Ismailia Governorate, Ismailia 11517, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh P.O. Box 71666, Saudi ArabiaDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Sinai University, Kantra 41636, EgyptTo achieve the best treatment of skin cancer, drug penetration inside the deepest layers of the skin is an important scientific interest. We designed an ethosome formulation that serves as a carrier for metformin and measured the in vitro skin permeation. We also aimed to measure the antitumor activity of the optimal ethosomal preparation when applied topically to chemically induced skin cancer in mice. We utilized a statistical Box–Behnken experimental design and applied three variables at three levels: lecithin concentration, cholesterol concentration and a mixture of ethanol and isopropyl alcohol concentrations. All formulations were prepared to calculate the entrapment efficiency %, zeta potential, size of the vesicles and drug release % after 1, 2, 4, 8 and 24 h. The size of the vesicles for the formulations was between 124 ± 14.2 nm and 560 ± 127 nm, while the entrapment efficiency was between 97.8 ± 0.23% and 99.4 ± 0.24%, and the drug release % after 8 h was between 38 ± 0.82% and 66 ± 0.52%. All formulations were introduced into the Box–Behnken software, which selected three formulations; then, one was assigned as an optimal formula. The in vivo antitumor activity of metformin-loaded ethosomal gel on skin cancer was greater than the antitumor activity of the gel preparation containing free metformin. Lower lecithin, high ethanol and isopropyl alcohol and moderate cholesterol contents improved the permeation rate. Overall, we can conclude that metformin-loaded ethosomes are a promising remedy for treating skin cancers, and more studies are warranted to approve this activity in other animal models of skin cancers.https://www.mdpi.com/1424-8247/15/6/657experimental skin cancerentrapment efficacyethosomesmetforminin vitro permeationzeta potential |
| spellingShingle | Ibrahim A. Mousa Taha M. Hammady Shadeed Gad Sawsan A. Zaitone Mohamed El-Sherbiny Ossama M. Sayed Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in Mice Pharmaceuticals experimental skin cancer entrapment efficacy ethosomes metformin in vitro permeation zeta potential |
| title | Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in Mice |
| title_full | Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in Mice |
| title_fullStr | Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in Mice |
| title_full_unstemmed | Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in Mice |
| title_short | Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in Mice |
| title_sort | formulation and characterization of metformin loaded ethosomes for topical application to experimentally induced skin cancer in mice |
| topic | experimental skin cancer entrapment efficacy ethosomes metformin in vitro permeation zeta potential |
| url | https://www.mdpi.com/1424-8247/15/6/657 |
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