Novel topical and transdermal delivery of colchicine with chitosan based biocomposite nanofiberous system; formulation, optimization, characterization, ex vivo skin deposition/permeation, and anti-melanoma evaluation

Abstract Melanoma bears the highest mortality rate in skin cancers. The unique properties of chitosan-based nanofibers provide a great potential to formulate an effective topical drug delivery system. With the emphasis on Colchicine systemic toxicity as an obstacle against the administration in systemic chemotherapy and considering its superiority over approved chemotherapeutic agents for melanoma management, it was chosen to be formulated in a nanofiber based topical drug delivery system. The optimization assay was conducted by AFM and SEM based on the morphology, topographic data, and mean diameter size of the nanofibers. Other characterization studies include FTIR, XRD, STA, contact angle measurement, tensile test, ex vivo skin permeation, deposition analysis, release kinetic and anti-melanoma efficiency against A-375 cell line. As a result, significant colchicine deposition in the skin with remarkable cytotoxicity against melanoma cell line makes it a desirable formulation to be administered as a topical or local reservoir system for neoadjuvant chemotherapy before other interventions and adjuvant therapy of tumors after surgery and, also, for other skin diseases with dose adjustment. Besides, the observed first order release kinetic behavior through the skin could suggest it as a transdermal colchicine delivery system which improves its efficiency in systemic indications.