Lipoplex-Mediated Deintercalation of Doxorubicin from Calf Thymus DNA–Doxorubicin Complex

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Abstract
In the current effort, we reported the lipoplex mediated deintercalation of anticancer drug doxorubicin (DOX) from DOX-DNA complex under controlled experimental conditions. We used three zwitterionic liposomes namely DPPC, DMPC and POPC which are widely different in their phase transition temperature to form lipoplex with calf thymus DNA in presence of Ca2+ ions. The study revealed that DPPC being in sol-gel phase is more effective in releasing drug from DOX-DNA complex compared to liposomes that remain in liquid crystalline phase (DMPC and POPC). The higher extent of drug release in case of DPPC liposomes was attributed to the stronger lipoplex formation with DNA as compared to other liposomes. Owing to the relatively smaller head group area, DPPC liposomes in its sol gel phase can absorb larger number of Ca2+ ions and hence offer strong electrostatic interaction towards DNA. This interaction was confirmed by the time resolved anisotropy and circular dichroism spectroscopy. Apart from the electrostatic interaction, the possible hydrophobic interaction between liposomes and DNA was also taken into account for the observed deintercalation. The successful up taking of drug molecules by liposomes in the post release period from drug-DNA complex was also confirmed by confocal laser scanning microscopy (CLSM).

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