Preparation and In Vitro characterization of metformin loaded polycaprolactone nanoparticle based gel formulation for the topical treatment of melanoma

Melanoma is one of the most challenging types of cancers to treat with a high metastatic capability. Resistance to chemotherapeutic drugs used in melanoma treatment leads to reduced treatment efficacy. Furthermore, systemic side effects can also occur with chemotherapeutic drugs, which can cause damage to healthy tissues. In addition to chemotherapy, radiotherapy, photodynamic therapy, and gene therapy are also applied in melanoma treatment. However, these methods have their advantages and disadvantages as well. Considering the poor prognosis and the shortcomings in treatment, innovative treatments are needed for melanoma. In this thesis, metformin HCl, a biguanide derivative antidiabetic drug that has shown anticancer activity in the literature, was chosen as the therapeutic agent. The aim of the study was to increase the skin retention after topical application by enabling the drug to be applied locally to the pathological area and encapsulating metformin into nanoparticles. Overcoming the stratum corneum, the outermost layer of the skin, is quite challenging in topical applications and limits treatment. In this thesis, metformin HCl (Met) was encapsulated in Polycaprolactone (PCL) nanoparticles to reduce particle size and enhance the penetration of the drug into the skin. Cell culture studies showed that the Chitosan (CS) gel formulation containing metformin HCl-loaded PCL nanoparticles was more effective compared to the gel containing free metformin. In vitro characterization studies and ex-vivo studies concluded that the chitosan gel formulation containing Met-loaded PCL nanoparticles is a promising system for the topical treatment of melanoma.