Chitosan Functionalized Skin-Adhesive Formulation for Ergotamine Delivery in Melanoma Treatment

This study develops a skin-penetrating drug delivery system of thiolated chitosan-lithocholic acid nanomicelles for the treatment of melanoma. In this regard, ergotamine was selected as a model drug in consideration of its possible antitumor activities. The resultant system shall not only reduce serious side effects associated with conventional cancer therapies, but it shall also aim to enhance drug penetration and retention with controlled release. The main goal was to develop thCS-LA nanomicelles with ergotamine for improved skin adhesion, mucopenetration, and drug release properties for the effective treatment of melanoma. Ergotamine-loaded thCS-LA nanomicelles were prepared and then subjected to various in vitro studies like drug release study, skin adhesion test, mucopenetration study, hemolysis test, and cell viability assay. Subsequently, this developed drug delivery system was applied and tested in a mouse model of cutaneous cancer. Characterization studies confirmed the successful formulation of thCS-LA nanomicelles, which demonstrated improved physicochemical properties, skin adhesion, and mucopenetration as compared to unmodified polymers. Moreover, in the in vitro release studies, higher release rates for ergotamine-loaded nanomicelles at pH 5.5, which relates to acidified conditions of the tumor microenvironment, were compared to the other pH values tested. Whereupon in vivo testing was conducted, the reduction of tumor size, the reduction of tumor weight, and the survival rate showed much better results for all groups of treatment. In other words, the current study successfully developed, characterized, and evaluated the thCS-LA nanomicelle drug delivery system loaded with ergotamine. Enhanced skin adhesion and mucopenetration improved the therapeutic outcome in the animal model due to the controlled release of the drug.