Hybrid Unilamellar Vesicles of Phospholipids and Block Copolymers with Crystalline Domains

Abstract

Phospholipid (PL) membranes are ubiquitous in nature and their phase behavior has been extensively studied. Lipids assemble in a variety of structures and external stimuli can activate a quick switch between them. Amphiphilic block copolymers (BCPs) can self-organize in analogous structures but are mechanically more robust and transformations are considerably slower. The combination of PL dynamical behavior with BCP chemical richness could lead to new materials for applications in bioinspired separation membranes and drug delivery. It is timely to underpin the phase behavior of these hybrid systems and a few recent studies have revealed that PL–BCP membranes display synergistic structural, phase-separation, and dynamical properties not seen in pure components. One example is phase-separation in the membrane plane, which seems to be strongly affected by the ability of the PL to form lamellar phases with ordered alkyl chains. In this paper we focus on a rather less explored design handle which is the crystalline properties of the BCP component. Using a combination of confocal laser scanning microscopy and X-ray scattering we show that hybrid membranes of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-b-PCL) display BCP-rich and PL-rich domains when the BCP comprises crystalline moieties. The packing of the hydrophilic part of the BCP (PEG) favors mixing of DPPC at the molecular level or into nanoscale domains while semi-crystalline and hydrophobic PCL moieties bolster microscopic domain formation in the hybrid membrane plane.

Aqueous Heat Method for the Preparation of Hybrid Lipid–Polymer Structures: From Preformulation Studies to Protein Delivery

“…The decrease or the abolishment of the pretransition leads to the conclusion that the hydrophilic polymeric chain also interacts with the polar groups of the lipids, causing a different orientation of the polar head due to the creation of hydrophilic interactions between PDMAEMA and DDA/TDB. In other words, the presence of the PLMA-b-PDMAEMA copolymer controls the molecular packing of the lipids by altering their physical liquid crystalline phase, dynamics, and phase separation [ 26 , 27 , 28 ].…”

Current Perspectives on Synthetic Compartments for Biomedical Applications

“…The formation of crystalline PCL and gel-like DPPC regions was confirmed through X-ray scattering and diffraction. These regions strongly influenced the PL membrane fluidity and order, indirectly influencing the mechanical and permeability properties of the membrane [ 73 ]. Polymer crystallinity plays an important role in the formation of heterogeneous membranes.…”

“…( A ) Cross-sectional micrograph of DPPC-mPEG- b -PCL GUVs stained via fluorescein isothiocyanate (FITC, on mPEG- b -PCL, green) and Liss Rhod PE (in DPPC, red). Adapted with permission from [ 73 ]. Copyright 2020 MDPI.…”

Recent Advancements in Polymer/Liposome Assembly for Drug Delivery: From Surface Modifications to Hybrid Vesicles

“…The type of structure that can be obtained depends on the compatibility between the lipid and polymeric building blocks in terms of dimensions and chemical–physical properties, as well as the polymers/lipids ratio. It is therefore possible to obtain very different types of vesicles, in which the limit forms have the polymeric molecules homogeneously distributed in the bilayer ( Figure 1 D, left) [ 22 , 26 , 27 ] or segregated in separate domains ( Figure 1 D, right). Although this last configuration has mainly been observed and studied in micrometric giant vesicles that have limited applications in the field of drug delivery [ 26 , 27 ], examples relating to nanostructured vesicles have also been reported [ 28 ].…”