Dendrimeric micelles composed of polyamidoamine dendrimer-peptide-cholesterol conjugates as drug carriers for the treatment of melanoma and bacterial infection

Abstract

Skin cancer is a serious health concern posing an economic burden. Phytochemicals isolated from plants have attracted the attention of researchers as potential therapeutic agents against skin cancer. Paclitaxel and curcumin are effective anticancer agents. However, their poor solubility in aqueous solutions results in low bioavailability, limiting their therapeutic applications. In this study, we developed dendrimeric micelles to encapsulate paclitaxel and curcumin for the treatment of melanoma. The antibacterial activity of curcumin-loaded dendrimeric micelles was evaluated. Dendrimeric micelles were prepared using PAMAM dendrimers conjugated with histidine-arginine dipeptides and cholesterol (PHRC). Different amounts of cholesterol (6 % or 23 %) were conjugated to the surface of PAMAM dendrimer generation 2 derivatives (PAMAM G2-HR) to evaluate the effects of cholesterol on the drug encapsulation efficiency and bioactivity. The critical aggregation concentration (CAC) value of PHRC6 and PHRC23 was 0.14 mg/mL and 0.09 mg/mL, respectively. The size of the dendrimeric micelles was confirmed using dynamic light scattering (DLS). Furthermore, the cytotoxicity of PHRC amphiphiles was measured in B16F10 melanoma cells. Both PHRC6 and PHRC23 were combined with TPGS to prepare functional mixed dendrimeric micelles, including PHRC6/TPGS and PHRC23/TPGS. The encapsulation efficiency was higher for curcumin than paclitaxel (80.2 % and 76.3 % for curcumin and 30.7 % and 38.2 % for paclitaxel in PHRC6/TPGS and PHRC23/TPGS, respectively). Based on these results, PHRC/TPGS dendrimeric micelles displayed a high potential for the nano-formulation of hydrophobic drugs and good bioavailability and bioactivity against skin cancer.