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

Abstract

In this paper, we report the lipoplex-mediated deintercalation of anticancer drug doxorubicin (DOX) from the DOX-DNA complex under controlled experimental conditions. We used three zwitterionic liposomes, namely, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC), which are widely different in their phase transition temperatures to form a lipoplex with calf thymus DNA in the presence of Ca(2+) ions. The study revealed that DPPC being in sol-gel phase was more effective in releasing the drug from the DOX-DNA complex compared with liposomes that remain in liquid crystalline phase (DMPC and POPC). The higher extent of drug release in the case of DPPC liposomes was attributed to the stronger lipoplex formation with DNA as compared with that of other liposomes. Owing to the relatively smaller head group area, the DPPC liposomes in their sol-gel phase can absorb a larger number of Ca(2+) ions and hence offer a strong electrostatic interaction with DNA. This interaction was confirmed by time-resolved anisotropy and circular dichroism spectroscopy. Apart from the electrostatic interaction, the possible hydrophobic interaction between the liposomes and DNA was also taken into account for the observed deintercalation. The successful uptake of drug molecules by liposomes from the drug-DNA complex in the post-release period was also confirmed using confocal laser scanning microscopy (CLSM).

Exploring the Nucleobase-Specific Hydrophobic Interaction of Cryptolepine Hydrate with RNA and Its Subsequent Sequestration

“…Looking at the cytotoxic properties of CRYP, the issue of sequestration of the intercalated drug naturally becomes important in order to develop safe therapeutic applications. , Successful sequestration of DNA-bound drugs has been reported by many groups through the formation of micelles or liposome vesicles. − Naturally, successful removal of bound drugs from the genetic materials is crucial in reducing their cytotoxic effects. − Herein, we attempted the application of host–guest chemistry to achieve deintercalation of the RNA-bound drug molecules . For the sequestration process, we used cucurbit[7]­uril (CB7), which serves as the host.…”

Influence of a Polyneurotransmitter on DNA-Mediated Förster-Based Resonance Energy Transfer: A Path Leading to White Light Generation

“…The most important genetic material present in mammals that carries all the genetic information and widely controls different physiological processes is coined as deoxyribonucleic acid (DNA). , Among the few varieties of DNA, the most common DNA is B-DNA, which is also called Watson–Crick DNA. , Although the DNA constituting base pairs exerts an extremely low extent of intrinsic fluorescence intensity and is also under excitation in the ultraviolet (UV) region (i.e., at 260 nm), there is a growing list of various extrinsic fluorescent molecules that bind with DNA with respective emission enhancement and are therefore utilized as a strong fluorescent DNA biomarker. − Now, among all these double helix binders, 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI) and ethidium bromide (EtBr) are two important fluorophores that have also been used in our present work. In this respect, it is important to disclose that DNA usually has two primary modes of binding, i.e., in the groove region (groove binding) and in between the base pairs (intercalation mode of binding).…”

“…The most important genetic material present in mammals that carries all the genetic information and widely controls different physiological processes is coined as deoxyribonucleic acid (DNA). 54,55 Among the few varieties of DNA, the most common DNA is B-DNA, which is also called Watson−Crick DNA. 54,55 Although the DNA constituting base pairs exerts an extremely low extent of intrinsic fluorescence intensity and is also under excitation in the ultraviolet (UV) region (i.e., at 260 nm), there is a growing list of various extrinsic fluorescent molecules that bind with DNA with respective emission enhancement and are therefore utilized as a strong fluorescent DNA biomarker.…”

Exploring the utility of hybrid siloxane-phosphocholine (SiPC) liposomes as drug delivery vehicles

“…34 Liposomes derived from hybrid SiPCs generally do not exhibit any detectable thermotropic phase transitions between 5 C and 60 C. The exception to this was the SiPC, which had stearic acid in the sn-1 position and displayed a phase transition temperature at 17 C. The absence of phase transitions suggests that SiPC liposomes are comparable to liposomes composed of phosphocholines (PCs) such as POPC, DOPC with unsaturated fatty acids, or the archaebacterial PC 1,2-diphytanoyl-sn-glycero-3phosphocholine (DPhyPC). [35][36][37][38] The suitability of articial liposomes for drug delivery purposes is largely dependent on the specic release kinetics of the bilayer. Transport across the bilayer is controlled by the polarity of the encapsulant, as well as the permeability and uidity of the liposomal bilayer, bilayer thickness, and the number of bilayers through which the drug must migrate.…”