Topical Delivery of Carvedilol Loaded Nano-Transfersomes for Skin Cancer Chemoprevention
The β-blocker carvedilol has been shown to prevent skin carcinogenesis in vitro and in vivo. Since systemic absorption of the β-blocker may cause cardiovascular disturbance, we developed a carvedilol loaded transfersome for skin-targeted delivery. Transfersomes were prepared using phospholipids and...
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MDPI AG
2020-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/12/1151 |
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| author | Mengbing Chen Md Abdullah Shamim Ayaz Shahid Steven Yeung Bradley T. Andresen Jeffrey Wang Vijaykumar Nekkanti Frank L. Meyskens Kristen M. Kelly Ying Huang |
| author_facet | Mengbing Chen Md Abdullah Shamim Ayaz Shahid Steven Yeung Bradley T. Andresen Jeffrey Wang Vijaykumar Nekkanti Frank L. Meyskens Kristen M. Kelly Ying Huang |
| author_sort | Mengbing Chen |
| collection | DOAJ |
| description | The β-blocker carvedilol has been shown to prevent skin carcinogenesis in vitro and in vivo. Since systemic absorption of the β-blocker may cause cardiovascular disturbance, we developed a carvedilol loaded transfersome for skin-targeted delivery. Transfersomes were prepared using phospholipids and surfactants at various ratios and characterized. One formulation (F18) selected for further analysis was composed of carvedilol, soy phosphatidylcholine, and Tween-80 at a ratio of 1:3:0.5, which had a particle size of 115.6 ± 8.7 nm, a zeta potential of 11.34 ± 0.67 mV, and an encapsulation efficiency of 93.7 ± 5.1%. F18 inhibited EGF-induced neoplastic transformation of mouse epidermal JB6 P+ cells at non-toxic concentrations, while only high concentrations induced cytotoxicity in JB6 P+ and human keratinocytes HaCaT. Compared to the free drug, F18 released through the dialysis membrane and permeated through the porcine ear skin at a slower rate, but similarly depositing the drug in the epidermis and dermis of the skin. Consistently, surface application of F18 on reconstructed full-thickness human skin showed slower drug permeation, while it suppressed ultraviolet-induced DNA damage, inflammatory gene expression, and apoptosis. These data indicate that transfersome is a promising topical delivery system of carvedilol for preventing ultraviolet-induced skin damage and carcinogenesis. |
| first_indexed | 2024-03-10T14:31:33Z |
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| id | doaj.art-ed49c9635b2845b5ab89447d4593eda0 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T14:31:33Z |
| publishDate | 2020-11-01 |
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| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-ed49c9635b2845b5ab89447d4593eda02023-11-20T22:33:47ZengMDPI AGPharmaceutics1999-49232020-11-011212115110.3390/pharmaceutics12121151Topical Delivery of Carvedilol Loaded Nano-Transfersomes for Skin Cancer ChemopreventionMengbing Chen0Md Abdullah Shamim1Ayaz Shahid2Steven Yeung3Bradley T. Andresen4Jeffrey Wang5Vijaykumar Nekkanti6Frank L. Meyskens7Kristen M. Kelly8Ying Huang9Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USADepartments of Medicine and Biological Chemistry, Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92868, USADepartment of Dermatology, University of California, Irvine, CA 92697, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USAThe β-blocker carvedilol has been shown to prevent skin carcinogenesis in vitro and in vivo. Since systemic absorption of the β-blocker may cause cardiovascular disturbance, we developed a carvedilol loaded transfersome for skin-targeted delivery. Transfersomes were prepared using phospholipids and surfactants at various ratios and characterized. One formulation (F18) selected for further analysis was composed of carvedilol, soy phosphatidylcholine, and Tween-80 at a ratio of 1:3:0.5, which had a particle size of 115.6 ± 8.7 nm, a zeta potential of 11.34 ± 0.67 mV, and an encapsulation efficiency of 93.7 ± 5.1%. F18 inhibited EGF-induced neoplastic transformation of mouse epidermal JB6 P+ cells at non-toxic concentrations, while only high concentrations induced cytotoxicity in JB6 P+ and human keratinocytes HaCaT. Compared to the free drug, F18 released through the dialysis membrane and permeated through the porcine ear skin at a slower rate, but similarly depositing the drug in the epidermis and dermis of the skin. Consistently, surface application of F18 on reconstructed full-thickness human skin showed slower drug permeation, while it suppressed ultraviolet-induced DNA damage, inflammatory gene expression, and apoptosis. These data indicate that transfersome is a promising topical delivery system of carvedilol for preventing ultraviolet-induced skin damage and carcinogenesis.https://www.mdpi.com/1999-4923/12/12/1151β-blockercarvedilolultravioletskin cancerchemopreventiontransfersome |
| spellingShingle | Mengbing Chen Md Abdullah Shamim Ayaz Shahid Steven Yeung Bradley T. Andresen Jeffrey Wang Vijaykumar Nekkanti Frank L. Meyskens Kristen M. Kelly Ying Huang Topical Delivery of Carvedilol Loaded Nano-Transfersomes for Skin Cancer Chemoprevention Pharmaceutics β-blocker carvedilol ultraviolet skin cancer chemoprevention transfersome |
| title | Topical Delivery of Carvedilol Loaded Nano-Transfersomes for Skin Cancer Chemoprevention |
| title_full | Topical Delivery of Carvedilol Loaded Nano-Transfersomes for Skin Cancer Chemoprevention |
| title_fullStr | Topical Delivery of Carvedilol Loaded Nano-Transfersomes for Skin Cancer Chemoprevention |
| title_full_unstemmed | Topical Delivery of Carvedilol Loaded Nano-Transfersomes for Skin Cancer Chemoprevention |
| title_short | Topical Delivery of Carvedilol Loaded Nano-Transfersomes for Skin Cancer Chemoprevention |
| title_sort | topical delivery of carvedilol loaded nano transfersomes for skin cancer chemoprevention |
| topic | β-blocker carvedilol ultraviolet skin cancer chemoprevention transfersome |
| url | https://www.mdpi.com/1999-4923/12/12/1151 |
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