Abstract
Malignant melanoma is the type of skin cancer that develops in the melanocytes and is the most aggressive type of skin cancer. The currently used first-line anit-melanoma treatment, Dacarbazine (Dac) intravenous injection is associated with poor and erratic gastric absorption, short half-life, instability, photosensitivity, adverse effects including pain at the administration site, nausea, hepatic toxicity, and development of chemoresistance. Quercetin (Qct) has been reported to have anti-melanoma activity along with reduction of the chemoresistance of Dac. Hence, a transdermal delivery system using both Qct and Dac would overcome many of the aforesaid challenges and deliver these drugs both locally and systemically useful for non-metasatsized and metastasized melanoma, respectively. However, the skin permeation of Dac and Qct is poor. Therefore, polymeric NPs loaded with Dac and Qct were prepared to enhance their skin permeation .Stable NPs (mean diameter of 252.1 ± 2.3 nm) of Dac and Qct were prepared using PLGA . In vitro release studies indicated ta burst release for Dac whereas Qct a slow and gradual release for Qct with a 100% release by 24 hours. On the other hand, no permeation was detected with the free drug which indicates the effectiveness of the NPs in enhancing the skin permeability. NPs also reduced the IC50 of both the drugs as provided by MTT assay indicating their potential to decrease the dose of Dac thereby its adverse effects. ECIS (Electrical Cell Substrate Impedance Sensing) measurements indicate that the combination of Dac and Qct has the potential to inhibit the migration of B16F10 melanocytes thereby preventing the metasatsis of melanoma. However, the drug loading was very low and Dac degraded after release and the release profile of both drugs was dissimilar. Therefore, future studies should include optimization of process parameters to achieve higher drug load and desired release pattern.