Mixing Block Copolymers with Phospholipids at the Nanoscale: From Hybrid Polymer/Lipid Wormlike Micelles to Vesicles Presenting Lipid Nanodomains (original) (raw)
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Hybrid polymer/lipid vesicles: state of the art and future perspectives
Materials Today, 2013
Hybrid vesicles resulting from the combined self-assembly of both amphiphilic copolymers and lipids have attracted particular interest from chemists and (bio)physicists over the last five years. Such assemblies may be viewed as an advanced vesicular structure compared to their liposome and polymersome forerunners as the best characteristics from the two different systems can be integrated in a new, single vesicle. To afford such a design, the different parameters controlling both self-assembly and membrane structure must be tuned. This highlight aims to present a comprehensive overview of the fundamental aspects related to these structures, and discuss emerging developments and future applications in this field of research.
Langmuir, 1999
The physical conjugation of (tri-) block copolymer molecules to phospholipid vesicle bilayers in order to construct sterically stabilized vesicles can be carried out in two different ways: by allowing the copolymer molecules to freely participate in the small unilamellar vesicle (SUV) formation process along with the lipids or by adding the copolymer molecules to pre-formed small unilamellar liposomes. Structurally and morphologically different copolymer coated vesicle systems occur. The effect on the mean vesicle diameter and the vesicle surface characteristics is monitored by dynamic light scattering and laser Doppler electrophoresis techniques for a wide variety of block copolymer molecules of the PEO-PPO-PEO type (PEO is poly(ethylene oxide); PPO poly(propylene oxide)). Systematic investigations as a function of copolymer added concentration and molecular structure were undertaken throughout. The results indicate a dramatic increase in mean vesicle diameter when the polymer molecules are present during vesiculation, while in the case of copolymer addition to already formed liposomes the mean vesicle size follows a classic Langmuirian-type adsorption curve as a function of copolymer concentration. The -potential values obtained decrease in a very similar pattern irrespective of the way of addition for the large PF127 (PEO99-PPO65-PEO99) molecule, illustrating the presence of polymer chains at the vesicle surface. For the small, more hydrophobic L61 (PEO10-PPO16-PEO10) molecule, the reduced -potential value is maintained only when the copolymer molecules participate in bilayer formation, indicating absence of interaction between the polymer and the lipids when added to preformed liposomes, due to the preferred copolymer tendency to aggregate into micelles separate from the lipid bilayer particles (that eventually leads to phase separation). According to the molecular models proposed to describe the occurring lipid-copolymer interactions, addition of copolymer molecules after liposomes have been formed leads to their adsorption onto the outer liposome surface, its effectiveness being dependent on the influence that the hydrophilic (PEO) and hydrophobic (PPO) blocks exert on the copolymer molecular behaviour. Copolymer-lipid coparticipation toward bilayer formation, at low added polymer concentrations, leads to PPO block protection by arranging along with the lipids as integral parts of the vesicle bilayer, hence anchoring the PEO chains that dangle in the aqueous solution onto the vesicles. Simple geometrical considerations are also included, reinforcing the theoretical feasibility of the described models. The latter type of physically conjugating polymer chains onto vesicle surfaces is proposed as an improved alternative to the weak adsorption of amphiphilic molecules and the cumbersome chemical modification of the lipid polar headgroups to confer steric protection to liposomal surfaces.
Phase Separation and Nanodomain Formation in Hybrid Polymer/Lipid Vesicles
ACS Macro Letters, 2015
Hybrid polymer/lipid large unilamellar vesicles (LUVs) were studied by small angle neutron scattering (SANS), time-resolved Forster resonance energy transfer (TR-FRET), and cryo-transmission electron microscopy (cryo-TEM). For the first time in hybrid vesicles, evidence for phase separation at the nanoscale was obtained, leading to the formation of stable nanodomains enriched either in lipid or polymer. This stability was allowed by using vesicle-forming copolymer with a membrane thickness close to the lipid bilayer thickness, thereby minimizing the hydrophobic mismatch at the domain periphery. Hybrid giant unilamellar vesicles (GUVs) with the same composition have been previously shown to be unstable and susceptible to fission, suggesting a role of curvature in the stabilization of nanodomains in these structures.
Langmuir
We investigated the influence of an n-alkyl-PEO polymer on the structure and dynamics of phospholipid vesicles. Multilayer formation and about a 9% increase in the size in vesicles were observed by cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), and small-angle neutron/X-ray scattering (SANS/SAXS). The results indicate a change in the lamellar structure of the vesicles by a partial disruption caused by polymer chains, which seems to correlate with about a 30% reduction in bending rigidity per unit bilayer, as revealed by neutron spin echo (NSE) spectroscopy. Also, a strong change in lipid tail relaxation was observed. Our results point to opportunities using synthetic polymers to control the structure and dynamics of membranes, with possible applications in technical materials and also in drug and nutraceutical delivery.
Polymers, 2020
In this work, we have used low-molecular-weight (PEG12-b-PCL6, PEG12-b-PCL9 or PEG16-b-PLA38; MW, 1.25–3.45 kDa) biodegradable block co-polymers to construct nano- and micron-scaled hybrid (polymer/lipid) vesicles, by solvent dispersion and electroformation methods, respectively. The hybrid vesicles exhibit physical properties (size, bilayer thickness and small molecule encapsulation) of a vesicular boundary, confirmed by cryogenic transmission electron microscopy, calcein leakage assay and dynamic light scattering. Importantly, we find that these low MW polymers, on their own, do not self-assemble into polymersomes at nano and micron scales. Using giant unilamellar vesicles (GUVs) model, their surface topographies are homogeneous, independent of cholesterol, suggesting more energetically favorable mixing of lipid and polymer. Despite this mixed topography with a bilayer thickness similar to that of a lipid bilayer, variation in surface topology is demonstrated using the interfacial...
Polymers
Liposomes are consolidated and attractive biomimetic nanocarriers widely used in the field of drug delivery. The structural versatility of liposomes has been exploited for the development of various carriers for the topical or systemic delivery of drugs and bioactive molecules, with the possibility of increasing their bioavailability and stability, and modulating and directing their release, while limiting the side effects at the same time. Nevertheless, first-generation vesicles suffer from some limitations including physical instability, short in vivo circulation lifetime, reduced payload, uncontrolled release properties, and low targeting abilities. Therefore, liposome preparation technology soon took advantage of the possibility of improving vesicle performance using both natural and synthetic polymers. Polymers can easily be synthesized in a controlled manner over a wide range of molecular weights and in a low dispersity range. Their properties are widely tunable and therefore ...
Interaction and Complexation of Phospholipid Vesicles and Triblock Copolymers
Mixtures of Pluronic (F-127 or L-61) and phospholipid were investigated for a wide range of Pluronic concentrations (0-15 wt %) using dynamic light scattering, differential scanning calorimetry, and fluorescence microscopy. The present study is aimed at better understanding how the amphiphilic triblock copolymers affect the lipid vesicles, particularly in the high-concentration regime. Our results show that L-61 interacts more strongly with phospholipid vesicles than F-127 when the copolymer is at the unimer state in the solution. For high concentrations, F-127 forms mixed micelles with solubilized lipid molecules in the form of bilayer patches. This novel behavior was observed for the first time. In contrast, more hydrophobic L-61 tends to precipitate with the solubilized lipids as large crew-cut mixed aggregates.
Chimeric lipid/block copolymer nanovesicles: Physico-chemical and bio-compatibility evaluation
European Journal of Pharmaceutics and Biopharmaceutics, 2016
Chimeric systems are mixed nanovectors composed by different in nature materials and exhibit new functionalities and properties. The particular chimeric nanovectors, formed by the co-assembly of low and high molecular weight amphiphiles, have the potential to be utilized as drug delivery platforms. We have utilized two lipids, L-αphosphatidylcholine, hydrogenated (Soy)(HSPC) and 1,2-dipalmitoyl-sn-glycero-3phosphocholine(DPPC), and a poly(oligoethylene glycol acrylate)-b-poly(lauryl acrylate) (POEGA-PLA) block copolymer, at different molar ratios, in aqueous media. Light scattering, differential scanning calorimetry (DSC) and imaging techniques (cryo-TEM, AFM) were employed in order to elucidate the structure and properties of the nanostructures, as well as the cooperativity between the components. DSC experiments showed considerable interaction of the block copolymer with the lipid bilayers and suggested an inhomogeneous distribution of the copolymer chains and lateral phase separation of the components. Vesicle formation was observed in most cases by cryo-TEM with a chimeric membrane exhibiting kinks, in accordance to DSC data. A series of biocompatibility experiments indicated good in vitro biological stability and low cytotoxicity in vivo of the novel nanocarriers. Finaly, ibuprofen (IBU) was used as model drug in order to study the loading and the release properties of the prepared chimeric lipid/block copolymer vesicles.
Novel dual VES phospholipid self-assembled liposomes with an extremely high drug loading efficiency
Colloids and surfaces. B, Biointerfaces, 2017
Vitamin E succinate (VES), a unique selective anti-cancer drug, has attracted much attention for its ability to induce apoptosis in various cancer cells. Importantly, it has been reported that VES is largely non-toxic to normal cells. However, poor aqueous solubility and bioavailability extensively restricted its clinical utility. In this report, dual VES phospholipid conjugate (di-VES-GPC) prodrug based liposomes were prepared in order to develop an efficient delivery system for VES. Di-VES-GPC was first synthesized by conjugating VES with l-α-glycerophosphorylcholine (GPC) using N,N'-dicyclohexylcarbodiimide (DCC) as a coupling agent. The di-VES-GPC prodrug was able to self-assemble into liposomes by reverse-phase evaporation method. The structure of the liposomes was characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and cryo-TEM. The results showed that di-VES-GPC assembled liposomes were spherical with an average diameter approximately 1...