Formation of Oxidation- and Acid-Sensitive Assemblies from Sterols and a Quaternary Ammonium Ferrocene Derivative: Quatsome- and Onion-like Vesicles and Extended Nanoribbons

Abstract

Quatsomes are a class of nonphospholipid vesicles in which bilayers are formed from mixtures of quaternary ammonium (QA) amphiphiles and sterols. We describe the formation of oxidation and acid-sensitive quatsome-like vesicles and other bilayer assemblies from mixtures of a ferrocenylated QA amphiphile (FTDMA) and several cholesterol derivatives. The influence of the sterol and the preparation method (extrusion or probe sonication) on the stability and morphology of the resulting vesicles is explored; a variety of structures can be obtained from small (ca. 30 nm) spherical unilamellar and oligolamellar quatsome-like vesicles to large (ca. 200 nm) multilamellar onion-like vesicles to extended nanoribbons many micrometers long. FTDMA-sterol vesicles undergo drastic shifts in vesicle and membrane structure when treated with a chemical oxidant (Frémy’s salt), a feature previously observed in liposomes containing FTDMA and now confirmed in nonphospholipid vesicles. Size distributions of spherical quatsome-like vesicles obtained from cryo-TEM are examined to estimate the membrane bending rigidity, and a hypothesis is presented to explain the underlying mechanism of the profound membrane alterations observed as a consequence of ferrocene oxidation.

Evaluation of Quatsome Morphology, Composition, and Stability for Pseudomonas aeruginosa Biofilm Eradication

“…6,7,16 They also enable good adsorption of encapsulated antibiotics and, with further chemical modifications, they could in principle achieve targeted release toward certain bacterial species such as acid-producing bacterial biofilms. 17,18 Using simple sonication, 5,19 thin film hydration, 20 or compressed fluid methods, 21,22 QSs can be routinely prepared with an average diameter smaller than 200 nm. During these preparation processes, however, some of the QAC and sterol materials will precipitate due to insufficient hydration or sonication.…”

“…Using simple sonication, , thin film hydration, or compressed fluid methods, , QSs can be routinely prepared with an average diameter smaller than 200 nm. During these preparation processes, however, some of the QAC and sterol materials will precipitate due to insufficient hydration or sonication.…”