Comparison of the interactions of daunorubicin in a free form and attached to single-walled carbon nanotubes with model lipid membranes

Abstract

SummaryIn this work the interactions of an anticancer drug daunorubicin (DNR) with model thiolipid layers composed of 1,2-dipalmitoyl-sn-glycero-3-phosphothioethanol (DPPTE) were investigated using Langmuir technique. The results obtained for a free drug were compared with the results recorded for DNR attached to SWCNTs as potential drug carrier. Langmuir studies of mixed DPPTE–SWCNTs-DNR monolayers showed that even at the highest investigated content of the nanotubes in the monolayer, the changes in the properties of DPPTE model membranes were not as significant as in case of the incorporation of a free drug, which resulted in a significant increase in the area per molecule and fluidization of the thiolipid layer. The presence of SWCNTs-DNR in the DPPTE monolayer at the air–water interface did not change the organization of the lipid molecules to such extent as the free drug, which may be explained by different types of interactions playing crucial role in these two types of systems. In the case of the interactions of free DNR the electrostatic attraction between positively charged drug and negatively charged DPPTE monolayer play the most important role, while in the case of SWCNTs-DNR adducts the hydrophobic interactions between nanotubes and acyl chains of the lipid seem to be prevailing. Electrochemical studies performed for supported model membranes containing the drug delivered in the two investigated forms revealed that the surface concentration of the drug-nanotube adduct in supported monolayers is comparable to the reported surface concentration of the free DNR incorporated into DPPTE monolayers on gold electrodes. Therefore, it may be concluded that the application of carbon nanotubes as potential DNR carrier allows for the incorporation of comparable amount of the drug into model membranes with simultaneous decrease in the negative changes in the membrane structure and organization, which is an important aspect in terms of side effects of the drug.

The Lysosomotropic Activity of Hydrophobic Weak Base Drugs is Mediated via Their Intercalation into the Lysosomal Membrane

“…Such high concentrations of positively charged drugs at the water-interface of the bilayer can alter the delicate electrostatic balance in the lipid headgroups, inducing repulsion between the choline groups of phospholipids and increasing the distance between neighbor lipids (area per lipid), which results in a marked increase in membrane fluidity [83]. The latter is in complete concordance with reports of increased membrane fluidity induced by SUN, SIR [22] and DNR [84], as well as with the observed LMP induced by LDs [85]. In both cases, the fluidization effect was pH-dependent, a finding that correlates with the current results, where the abundance of LDs at the water/membrane interface was more prominent at acidic pH, where all compounds have the highest charge due to immediate protonation.…”

Doubly Stimulated Corrole for Organelle-Selective Antitumor Cytotoxicity

“…Hence, these findings confirm that PC-Im enhanced lysosomal fusion, resulting in rapid enlargement of lysosomes and decreased numbers of lysosomes per cell. Taking together the key role of membrane fluidity in the fusion of cells and organelles , along with several publications that demonstrated increased lysosomal membrane fluidity upon treatment with lysosomotropic agents, , we propose that PC-Im accumulates in the membrane of lysosomes where it induces increased membrane fluidity, resulting in enhanced lysosomal fusion. Since fusion processes rely on SNAREs, some of which depend on calcium, we further considered that upon lysosomal accumulation of PC-Im , calcium is released from lysosomes, thereby enhancing lysosome fusion via lysosomal SNAREs. − An attractive possibility is that upon accumulation of PC-Im in the membrane of lysosomes, and to a lesser extent in the membranes of the ER and Golgi apparatus, PC-Im provokes enhanced membrane fluidity and calcium leakage to the cytoplasm.…”

Development and Characterization of DOPEPEG2000 Coated Oleic Acid Liposomes Encapsulating Anticancer Drugs

“…The loading of active ingredients in liposomes can ensure optimum efficacy, enhance specific targeting and reduce toxicity. Liposomes can carry both lipophilic and hydrophilic drugs which can improve the efficiency of the treatment [24]. In this study, four anticancer drugs were selected based on their log P values ranging from log P = -3 to log P = ?…”