Effective Penetration of a Liposomal Formulation of Bleomycin through Ex-Vivo Skin Explants from Two Different Species.
Abstract: Bleomycin is a chemotherapy agent that, when administered systemically, can cause severe pulmonary toxicity. Bleosome is a novel formulation of bleomycin encapsulated in ultra-deformable (UD) liposomes that may be applicable as a topical chemotherapy for diseases such as non-melanoma skin cancer. To date, the ability of Bleosome to effectively penetrate through the skin has not been evaluated. In this study, we investigated the ability of Bleosome to penetrate through ex vivo skin explants from dogs and horses. We visualized the penetration of UD liposomes through the skin by transmission electron microscopy. However, to effectively image the drug itself we fluorescently labeled bleomycin prior to encapsulation within liposomes and utilized multiphoton microscopy. We showed that UD liposomes do not penetrate beyond the stratum corneum, whereas bleomycin is released from UD liposomes and can penetrate to the deeper layers of the epidermis. This is the first study to show that Bleosome can effectively penetrate through the skin. We speculate that UD liposomes are penetration enhancers in that UD liposomes carry bleomycin through the outer skin to the stratum corneum and then release the drug, allowing diffusion into the deeper layers. Our results are comparative in dogs and horses and warrant further studies on the efficacy of Bleosome as topical treatment.
Publication Date: 2022-02-21 PubMed ID: 35205831PubMed Central: PMC8870439DOI: 10.3390/cancers14041083Google Scholar: Lookup
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Summary
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The research article describes a study which investigated the effectiveness of a liposomal formulation of the chemotherapy agent bleomycin, known as Bleosome, in penetrating the skin of dogs and horses. The results indicated that while the liposomal carrier did not penetrate beyond the skin’s outer layer, bleomycin was still able to reach deeper epidermal layers.
Introduction and Background
- The study centered around Bleosome, a novel formulation of bleomycin encapsulated in ultra-deformable liposomes. Bleomycin is a chemotherapy agent, which when administered systemically, can lead to severe pulmonary toxicity. Researchers explored Bleosome as a possible topical chemotherapy treatment for non-melanoma skin cancer.
- The ability of Bleosome to successfully penetrate the skin had not been evaluated prior to this study. This research aimed to fill that knowledge gap by testing the penetration of Bleosome on ex vivo skin explants from dogs and horses.
Methodology
- Transmission electron microscopy was used to observe the penetration of ultra-deformable liposomes through the skin. This method enabled the researchers to visualize the mechanisms at play.
- In order to effectively observe the drug itself, the researchers labeled the bleomycin with fluorescent markers before encapsulating it within the liposomes. They then used multiphoton microscopy to track its movement.
Results
- The study found that the ultra-deformable liposomes themselves do not penetrate beyond the stratum corneum, which is the outermost layer of the skin. This layer primarily acts as a barrier to protect the underlying tissue from infection, dehydration, chemicals, and mechanical stress.
- However, the researchers discovered that bleomycin is effectively released from the ultra-deformable liposomes and is able to penetrate into the deeper layers of the epidermis. This result indicates that the Bleosome formulation could be an effective delivery method.
Conclusion and Future Research
- This study was the first to demonstrate that Bleosome can effectively penetrate the skin. The research team speculated that ultra-deformable liposomes could act as penetration enhancers. By this theory, the liposomes carry the bleomycin to the stratum corneum, release the drug there, and then the drug diffuses into the deeper epidermal layers.
- The results were comparable in dogs and horses, indicating that the same process may occur in different species. The conclusion of the study therefore, suggests future research to explore further the efficacy of Bleosome as a topical treatment.
Cite This Article
APA
Ferrari G, Pang LY, De Moliner F, Vendrell M, Reardon RJM, Higgins AJ, Chopra S, Argyle DJ.
(2022).
Effective Penetration of a Liposomal Formulation of Bleomycin through Ex-Vivo Skin Explants from Two Different Species.
Cancers (Basel), 14(4), 1083.
https://doi.org/10.3390/cancers14041083 Publication
Researcher Affiliations
- Roslin Institute, The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, UK.
- Roslin Institute, The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, UK.
- Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
- Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
- Roslin Institute, The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, UK.
- The London Dermatology Centre, London W1G 8AS, UK.
- The London Dermatology Centre, London W1G 8AS, UK.
- Roslin Institute, The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, UK.
Grant Funding
- N/A / SPS ANIMAL CARE
Conflict of Interest Statement
S.C. and A.J.H. are directors of SPS Animal Care Ltd., which partially funded this project. Regular meetings were held to discuss the results. However, the funders had no role in design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The other authors declare no conflict of interest.
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Citations
This article has been cited 1 times.- Queiroga F, Cogliati B. Translational and Comparative Research on Innovative Anti-Cancer Therapies.. Cancers (Basel) 2023 Feb 20;15(4).
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