Capacious and programmable multi-liposomal carriers

Abstract

Spherical polycationic brushes (SPBs) were synthesized by grafting polycationic chains onto 100 nm polystyrene particles. These particles were exposed to unilamellar egg-lecithin (EL) liposomes with a mean diameter of 40 nm that had been rendered anionic via the presence of 10 molar% of phosphatidylserine (PS(1-)). The liposomes also contained 30 mole% of a morpholinocyclohexanol-based lipid (MOCH) that undergoes a conformational flip when the pH is decreased from 7.0 to 5.0. Mixtures of SPBs and liposomes at pH 7 gave an electrostatically-driven complex possessing, on average, about 40 liposomes for each SPB particle. It was found that the bound liposomes rapidly release much of their contents when the pH is reduced from 7.0 to 5.0 owing mostly to a MOCH conformational change that creates defects in the bilayer membrane. The drop in pH does not, however, induce a separation of the liposomes from the SPBs. Around 50-60% of the liposome contents escape before, it is reasoned, lateral and transmembrane motion of the membrane components heals the defects and prevents further release. Remarkably, the liposomes complexed with SPB release their cargo much faster than the identical but non-complexed liposomes.

Calcium‐Responsive Liposomes via a Synthetic Lipid Switch

“…For example, Leblond and co‐workers reported a bis‐(methoxyphenyl)pyridine system in which protonation of the central pyridine nitrogen leads to rotation of methoxyphenyl groups to promote hydrogen bonding, thereby disrupting the membrane and triggering release . Additionally, Menger and co‐workers reported a morpholinocyclohexanol‐ (MOCH)‐lipid that undergoes a cyclohexanol chair flip upon morpholine protonation to help trigger release when the liposomes are tethered to spherical polycationic brushes . Regarding release driven by binding interactions, Smith and co‐workers utilized a sensor that targets the lipid phosphatidylserine (PS) to trigger release from liposomes containing PS .…”

Amino‐terminated polylactide micelles with an external poly(ethylene oxide) corona as carriers of drug‐loaded anionic liposomes

“…The number of liposomes capable of complexing with a single particle ( N ) was estimated using a relation derived earlier: where C lip is the lipid concentration at saturation (0.2 mg mL −1 ), S 1 is the mean surface area per lipid molecule or 0.7 nm 2 , d is the diameter of liposomes, M is the mean molecular weight of lipid, C car is the carrier (PLAM) concentration, D is the diameter of the polylactide core and ρ is its density, and N A is the Avogadro number. Substituting the experimental values and literature data into Eqn (1) gave N = 30, which is to say that an average of 30 liposomes bind to each polylactide micelle.…”

Lipid Switches: Stimuli‐Responsive Liposomes through Conformational Isomerism Driven by Molecular Recognition

“…In addition, cryo‐EM studies showed considerable membrane defects and budding at lower pH. In work since this initial report, the basicity of the amine group has been varied, the mechanistic details of release have been further studied, incorporation into liposomes has been shown to enhance gene delivery, libraries of compounds with different properties have been studied and compared, and this system has been combined with spherical polycationic brushes for pH‐driven release from these nanoparticles …”

“…In work since this initial report, the basicity of the amine group has been varied, [10] the mechanistic details of release have been further studied, [11] incorporation into liposomes hasbeen shown to enhance gene delivery, [12] libraries of compounds with different properties have been studied and compared, [13] and this system has been combined with spherical polycationic brushes for pH-driven releasefrom these nanoparticles. [14] LeBlond and co-workersh ave investigated pH-responsive lipid switchesb ased on ad i(methoxyphenyl)pyridine scaffold. [15] These wered esigned such that protonation of pyridine of initial conformer 2a would trigger rotation of the substituted anisole rings resultingi nh ydrogen bonding betweent he methoxya nd pyridinium groups in 2b (Scheme 3).…”