Preparation of chitosan nanoparticles for simultaneous drug delivery of dacarbazine and enoxaparin in melanoma

Abstract

The aim of this study was to investigate the anti-melanoma and anti-angiogenic effects of enoxaparin surface-coated dacarbazine-loaded chitosan nanoparticles (Enox-Dac-Chi NPs). The prepared Enox-Dac-Chi NPs had a particle size of 367.95 +/- 1.84 nm, zeta potential of-7.12 +/- 0.25 mV, efficiency of drug loading (DL) of 73.90 +/- 3.84 , and attached enoxaparin percentage of 98.53 +/- 0.96 . Both drugs had extended-release profiles and approximately 96 of enoxaparin and 67 dacarbazine were released within 8 h. The Enox-Dac-Chi NPs with IC50 of 59.60 +/- 1.25 mu g/ml were the most cytotoxic against melanoma cancer cells compared with chitosan nanoparticles containing only dacarbazine (Dac-Chi NPs) and free dacarbazine. There was no significant dif-ference between the cellular uptake of Chi NPs and enoxaparin coated Chi NPs (Enox-Chi NPs) in B16F10 cells. Enox-Chi NPs with an average anti-angiogenic score of 1.75 +/- 0.125 had more anti-angiogenic effect than enoxaparin. The results showed that simultaneous delivery of dacarbazine and enoxaparin by chitosan nano-particles can enhance the anti-melanoma effect of dacarbazine. Additionally, enoxaparin can prevent the mel-anoma metastasis by its anti-angiogenic activity. Thus, the designed nanoparticles can be introduced as effective drug delivery vehicles for the treatment and prevention of metastatic melanoma.