Three-Dimensional Microphase Separation and Synergistic Permeability in Stacked Lipid–Polymer Hybrid Membranes

Abstract

We present new structures of soft-material thin films that augment the functionality of substrate-mediated delivery systems. A hybrid material composed of phospholipids and block copolymers adopts a multilayered membrane structure supported on a solid surface. The hybrid films comprise intentional intramembrane heterogeneities that register across multilayers. These stacked domains convey unprecedented enhancement and control of permeability of solutes across micrometer-thick films. Using grazing incidence X-ray scattering, phase contrast atomic force microscopy, and confocal microscopy, we observed that in each lamella, lipid and polymers partition unevenly within the membrane plane segregating into lipid- or polymer-rich domains. Interestingly, we found evidence that like-domains align in registry across multilayers, thereby making phase separation three-dimensional. Phase boundaries exist over extended length scales to compensate the height mismatch between lipid and polymer molecules. We show that microphase separation in hybrid films can be exploited to augment the capability of drug-eluting substrates. Lipid–polymer hybrid films loaded with paclitaxel show synergistic permeability of drug compared to single-component counterparts. We present a thorough structural study of stacked lipid–polymer hybrid membranes and propose that the presence of registered domains and domain boundaries impart enhanced drug release functionality. This work offers new perspectives in designing thin films for controlled delivery applications.

Hybrid Unilamellar Vesicles of Phospholipids and Block Copolymers with Crystalline Domains

“…To understand the self-assembly and molecular organization of mPEG-b-PCL and DPPC within a hybrid membrane we performed structural studies using Small and Wide Angle X-ray scattering (SAXS/WAXS). While PL alkyl chain packing has been investigated in PL-BCP hybrid membranes before [6,12,[14][15][16], in nearly all systems studied so far the BCP component remains amorphous. In this paper, we wanted to investigate the behavior of a PL-BCP hybrid membrane when the BCP component has the ability to crystallize.…”

“…In the recent years, hybrid PL–BCP membranes have indeed emerged [ 6 , 7 , 9 , 10 , 11 , 12 ] as materials where the combined properties are not merely an additive of those observed in pure components. For example, the dynamics of alkyl chain conformational changes in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membranes are enhanced at room temperature by hybridization with poly(butadiene)- b -poly(ethylene oxide)—PBD-PEO BCPs [ 6 , 12 ]. In addition, DPPC membranes in the gel-phase (L β ) hybridized with PBD-PEO in a giant unilamellar vesicle (GUV) exhibit the formation of large phase-separated PL-rich and BCP-rich domains [ 13 ].…”

Large and Giant Unilamellar Vesicle(s) Obtained by Self-Assembly of Poly(dimethylsiloxane)-b-poly(ethylene oxide) Diblock Copolymers, Membrane Properties and Preliminary Investigation of Their Ability to Form Hybrid Polymer/Lipid Vesicles

“…Thus far, relatively little information is available about the structure, chemical nature, and molar mass of copolymers that could mix ideally with phospholipids. Most commonly, poly(butadiene) [3][4][5][6][7][8][9][10][11][12] and poly(dimethylsiloxane) [13][14][15][16][17][18][19][20] have been used as hydrophobic block, while studies with poly(isobutene) [21][22][23], poly(caprolactone) [24,25], poly(isoprene) [26], and poly(laurylacrylate) [27] have also been reported. Poly(ethylene oxide) is by far the most used hydrophilic block, although few studies report the use of hydrophilic thermo-responsive blocks such as poly(2-isopropyl-2-oxazoline) [28] and poly(ethylene glycoldiacrylate) [27].…”

Graphene-based sensing of oxygen transport through pulmonary membranes

“…In this respect, it is imperative to obtain uniform lung membrane film thickness. We have shown that lipid film thickness, even for complex mixtures, can be controlled by spin-coating speed [45][46][47] . The thickness and morphology of lung membranes can be determined by AFM using the tip-scratch method (Fig.…”