Triggered Instability of Liposomes Bound to Hydrophobically Modified Core−Shell PNIPAM Hydrogel Beads

Abstract

The ability to trigger a destabilization of the membrane integrity of liposomes bound to environmentally sensitive hydrophobically modified core-shell hydrogel beads is demonstrated. Hydrogel beads with a core composed of poly(N-isopropylacrylamide) lightly cross-linked with bisacrylamide (BA) (pNIPAM) and a shell composed of NIPAM highly cross-linked with BA and containing varying amounts of acrylic acid (AA) [p(NIPAM-co-AA)] undergo a volume phase transition (VPT) at approximately 32 degrees C, as determined from (1)H magic angle spinning (MAS) NMR, regardless of the AA content of the shell. When the shell was hydrophobically modified with either decylamine or tetradecylamine, binding of extruded large unilamellar vesicles (eLUVs) composed of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) was quantitative, as determined via fluorescence spectroscopy. Fluorescence microscopy showed that such bound eLUVs did not fuse. Hydrogel-bound eLUV membrane permeability was assessed using (31)P MAS NMR in the presence of the chemical shift agent praseodymium and demonstrated that only at lower degrees of hydrophobic modification of the core-shell hydrogels was eLUV membrane barrier integrity maintained when T < VPT. At a low degree of hydrophobic modification, cycling the temperature above the VPT even for short periods caused the eLUV membranes to become leaky. Hence, eLUV membrane permeability was coupled to the hydrogel VPT, a situation that would be useful in applications requiring triggered release of liposomal contents.

Fabrication and characterization of anisotropic nanofiber scaffolds for advanced drug delivery systems

“…43 In addition, thermoresponsive poly(NIPAM) core-shell microstructures, where the shell was highly modified with hydrophobic long alkyl chains, were stabilized when exposed to water. 44 In this respect, totally dissimilar jetting solutions separately containing 1) thermoresponsive and physically crosslinkable poly(NIPAM-co-SA), and 2) nonthermoresponsive and UV-initiated, chemically crosslinkable PEGDMA, were EHD cojetted by maintaining balanced rheological properties and fluid dynamics of both solutions, resulting in the formation of bicompartmental nanofibers with distinct compartments for stimuli-responsive actuation.…”

Lipobeads

“…It was shown (Figure 10) that a collapse of the hydrophobically modified PNIPA microgels within the lipid bilayer caused a shape change of the lipobeads from sphere (below T V ) to a small central core with high curvature protrusions (above T V ), consisting of the excess lipid bilayer which still adjoin the lipid bilayer remaining bound to the hydrogel via hydrophobic anchors [25,28]. Importantly, these changes were found to be reversible, and the bilayer remained intact and impermeable.…”

“…In this case, lipid bilayer adsorption on the surface of hydrogel particles prepared separately was promoted via Coulombic attraction between the charged microgels and oppositely charged lipids [7,23,24], hydration of lipid films with micro-or nanogel suspension [2,3], introduction of hydrophobic anchors at the microgel surface around which adsorbing lipids may assemble [6,[25][26][27][28], centrifugation of microgels onto a lipid film [29], microfluidic flowing [21], and emulsification [30][31][32].…”

“…In the absence of an added surfactant, the method is called precipitation polymerization. With the latter two methods, the lipobeads of 1-μm diameter are produced [2,7,23,25,28,31]. To prepare giant lipobeads with a diameter up to 100 μm, the inverse suspension polymerization (ISP) method is commonly applied [6,24,35,[43][44][45].…”

“…Unilamellarity, continuity, and nonleakiness of the lipid bilayer formed upon microgel/liposome mixing were proven for the micrometer-sized, hydrophobically modified, pNIPAM/p(NIPAMco-AA) core-shell hydrogel spheres [25,28]. It was also demonstrated by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM) [40] that hydrophobic modification of the nanogels is not required for spontaneous formation of the bilayer on their surface.…”