Effective Penetration of a Liposomal Formulation of Bleomycin through Ex-Vivo Skin Explants from Two Different Species

SIMPLE SUMMARY: Bleomycin, a chemotherapy drug, is currently injected into patients, but this can damage healthy tissues. Ideally, we would like to apply bleomycin directly onto a skin tumour but bleomycin is a big molecule and cannot pass through the skin or directly enter into cancer cells to kill them. Therefore, we need to find new ways of packaging the drug to get it inside cancer cells. Liposomes are small artificial bubbles made of from the same building blocks as our skin and cell membranes that can be filled with pharmaceutical drugs. In this study we propose that liposomes can assist with the delivery of bleomycin by improving penetration through the skin. We are using a new compound called Bleosome, which contains liposomes packed with bleomycin. We found that Bleosome penetrated more through the healthy skin of dogs and horses than bleomycin. These are promising results, indicating that Bleosome may be an effective treatment, with easy application and limited side-effects, to treat skin cancer. 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.