1-palmitoyl-2-oleoylphosphatidylcholine and acrylic-acid

We have fabricated Lipogels consisting of a single POPC lipid bilayer supported by a micrometer-sized, thermoresponsive, hydrophobically modified (HM), hydrogel sphere. The hydrogel consists of a lightly cross-linked poly(N-isopropylacrylamide) (pNIPAM) core surrounded by a highly cross-linked acrylic acid (AA)-rich p(NIPAM-co-AA) shell. The lipid bilayer was assembled by binding liposomes to HM microgels, followed by several cycles of freeze-thaw. The pNIPAM volume phase transition (VPT) at ∼32 °C was present both before and after hydrophobic modification and after lipid bilayer coating. Fluorescence studies confirmed the fusion of liposomes into a continuous single bilayer. At a temperature above the VPT, it was found that the volume decrease in the hydrogel was coupled to the appearance of highly curved obtrusions of the uncompromised lipid bilayer into the surroundings. It is anticipated that these properties of Lipogels will prove to be useful in drug delivery applications and in fundamental biophysical studies of membranes.

Topics: Acrylamides; Acrylates; Acrylic Resins; Drug Delivery Systems; Fluorescent Dyes; Freezing; Hydrogels; Lipid Bilayers; Liposomes; Magnetic Resonance Spectroscopy; Microspheres; Phase Transition; Phosphatidylcholines; Polymers; Spectrometry, Fluorescence; Temperature

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.

Topics: Acrylamides; Acrylates; Acrylic Resins; Hydrogel, Polyethylene Glycol Dimethacrylate; Liposomes; Magnetic Resonance Spectroscopy; Models, Theoretical; Phosphatidylcholines; Polymers