Amphiphilic drug interactions with model cellular membranes are influenced by lipid chain-melting temperature

Abstract

Small-molecule amphiphilic species such as many drug molecules frequently exhibit low-to-negligible aqueous solubility, and generally have no identified transport proteins assisting their distribution, yet are able to rapidly penetrate significant distances into patient tissue and even cross the blood–brain barrier. Previous work has identified a mechanism of translocation driven by acid-catalysed lipid hydrolysis of biological membranes, a process which is catalysed by the presence of cationic amphiphilic drug molecules. In this study, the interactions of raclopride, a model amphiphilic drug, were investigated with mixtures of biologically relevant lipids across a range of compositions, revealing the influence of the chain-melting temperature of the lipids upon the rate of acyl hydrolysis.

Andrographolide effect on both Plasmodium falciparum infected and non infected RBCs membranes

“…So inhibition of merozoite invasion may be attributed to the potential of andrographolide to disturb the proper flow of these steps. Such action has come in coincidence with results of the osmotic fragility test that showed a prominent loss of aptitude of the andrographolide treated RBCs to resist the hypotonicity induced spherocytosis [17,18,20].…”

“…Furthermore, it inhibits IL2, TNF-a production in immune cells [8] . Due to their amphipathic nature, terpenoides are expected to accumulate in membranous structures resulting in a loss of their integrity and ease their disruption during stressful situations [17,18] . Although moderate concentrations of andrographolide failed to induce RBCs hemolysis in the isotonic environment, its adverse impact on RBCs membrane was more obvious when the latter was incubated in a hypotonic environment.…”

Ratiometric NOE(−1.6) contrast in brain tumors

“…Supporting Figure S7 shows that NOE(−3.5) may arise from both proteins and methylene protons of membrane phospholipids, while NOE(−1.6) may arise from the phospholipid choline head groups that have a resonance frequency at around −1.6 ppm. The NOE(−1.6) coupling rate may depend on the choline head group mobility, which may be regulated by the phospholipid head group conformation and charge, membrane component, and insertion of small amphiphilic molecules into lipid bilayers . The NOE(−1.6) effect may also be relayed between successive protons through multiple‐step spin diffusion.…”

Cytotoxicity of polycations: Relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity

“…This induces the formation of inverted hexagonal phases in the lipid bilayer ("pores") and phase separation of lysophospholipids which form blebs, this being demonstrated for low molecular weight cationic materials. (Baciu et al, 2006;Casey et al, 2014;Casey, 2011;G.C. Shearman and Templer, 2007) The latter requires the cationic polymer to stabilise a pore, and thus remain localised in the pore.…”