Carrier in carrier: catanionic vesicles based on amphiphilic cyclodextrins complexed with DNA as nanocarriers of doxorubicin

Abstract

Doxorubicin (Dox) is a very effective chemotherapeutic agent; however, it can induce various side effects on normal tissues because of their non-specific distribution in the body. Therefore, there is an urgent demand to develop systems to successfully carry drugs to the desired sites of therapeutic action while reducing side effects. The aim of this study was to evaluate the interaction between catanionic vesicles based on amphiphilic cyclodextrins (ModCBHD) and DNA–Dox complex as a supramolecular anticancer drugs carrier (ModCBHD-DNA-Dox). The complexes were characterized by dynamic light scattering (DLS), zeta potential (ζ), circular dichroism (CD), emission spectroscopy, atomic force microscope (AFM), transmission electron microscopy (TEM). The results showed that ModCBHD vesicles exhibit a positive surface charge that allows negatively charged DNA-Dox to wrap them. Besides, Dox interacts with DNA through intercalation of the tetracene ring system and by ionic interaction through the amino sugar residue of the drug. In addition, ModCBHD-DNA-Dox exhibit a small particle size and optimal monodisperse size distribution that can take advantage of the enhanced permeability and retention (EPR) effect in cancer therapy. In vitro release of Dox from ModCBHD-DNA-Dox was slower than from DNA–Dox, due to the increasing appearance of external complexes formed from partially intercalated Dox after all the available sites become occupied upon addition of ModCBHD. The study overall highlighted a novel strategy that combine vesicles prepared from amphiphilic cyclodextrins and DNA that can be used as alternative carriers for chemotherapeutic agents such as Dox with slow-release properties.