Drug-carrier interaction analysis in the cell penetrating peptide-modified liposomes for doxorubicin loading

Doxorubicin (DOX) is widely used as an antitumor model drug in liposomes because of its high encapsulation efficiency. The cell-penetrating peptide (CPP) has potential applications in drug delivery systems. However, we discovered that the encapsulation efficiency of DOX decreased with increasing modification density of CPP on liposomes. To explore the interaction mechanisms of CPP-modified liposomes (CPPL) for DOX loading, X-ray diffraction, Fourier transform infrared spectroscopy and Raman spectroscopy were utilised, and theoretical calculations based on molecular dynamics simulation were performed. Results showed that the monomeric intermolecular interaction between CPP and DOX, in which the guanidinium group of CPP was parallel to the planar aromatic chromophore of DOX, depending on the cation-pi interaction and hydrogen bonds, weakened the tendency of DOX transporting into the internal medium from the liposomal external medium. Analysis of the interaction between CPP and DOX at the molecular level provided theoretical guidance for the further development of CPPL.