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 μg/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 difference 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 nanoparticles can enhance the anti-melanoma effect of dacarbazine. Additionally, enoxaparin can prevent the melanoma 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.

Keywords: Chitosan; Dacarbazine; Enoxaparin; Low-molecular-weight heparin; Melanoma; Nanoparticles.