Development of a hybrid peptide dendrimer micellar carrier system and its application in the reformulation of a hydrophobic therapeutic agent derived from traditional Chinese medicine

Abstract

The discovery that a cane toad poison-derived steroid, bufalin can significantly impact cancer cell proliferation supports its potential use in cancer therapy. However, its poor aqueous solubility and tissue deposition characteristics hamper its broader application as an anticancer therapeutic agent in its own right. To address this we developed an amphiphilic dendrimer-based delivery system, which self-assembles into discrete micelles in an aqueous environment. The bufalin–micelle inclusion complex was prepared by the co-precipitation method and their presence was confirmed by dynamic light scattering (DLS), zeta potential and differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) measurements. The self-assembled bufalin-containing micelles were found to form at/above the dendrimer concentration of 105.38 μmol L⁻¹, and showed a more than threefold increase in the aqueous solubility (142.9 μg mL⁻¹) of bufalin, when compared with a saturated bufalin aqueous solution (42.4 μg mL⁻¹), and two non-assembling peptides of similar composition (79.3 and 62.5 μg mL⁻¹ respectively).