Synthesis of Bilayer-Coated Nanogels by Selective Cross-Linking of Monomers inside Liposomes

Abstract

In this study, bilayer-coated polyacrylamide hydrogel nanoparticles were prepared by photoinitiated polymerization of acrylamide (AA) and bis(acrylamide) (BA) in the inner compartment of liposomes. The liposomes were formed in AA/BA solutions from lipid/Triton X-100 (TX100) mixed micelles by adsorption of TX100 to Bio-Beads SM2 and were studied by dynamic light scattering and transmission electron microscopy. The hydrodynamic diameters of the liposomes were ∼100 nm with low polydispersity. Addition of ascorbic acid before photopolymerization prevented macroscopic hydrogel formation by inhibition of free-radical polymerization of nonencapsulated monomers. Bare nanogel particles were finally obtained by removal of the lipid bilayer. As opposed to the commonly used dilution method, this convenient and versatile method of nanogel synthesis will allow incorporation of membrane proteins in the bilayer and the use of monomers that readily pass the lipid membrane.

Lipobeads

“…First of all, encapsulation of hydrogel-forming components into liposomes can result from hydration of lipid cast film formed upon solvent evaporation [1,2,5,9,11,13,14,16,32], electroformation [12,22,33,34], or rapid phase evaporation [19,20]. The size of liposomes ensures the final size of lipobeads.…”

“…For 100-nm lipobeads, the liposomal formulations have to be sonicated [1,9] or extruded through a nanopore filter of a needed pore size [5,8,11,14,16,19,32]. Another approach to control the size of pre-lipobeads is based on hydrodynamic focusing of a stream of the liposome precursor solution by the flow of a hydrogel-forming solution within a microfluidic device [21].…”

“…filtration [1,21], centrifugation and dialysis [5,13,20,30], or introduction of polymerization scavengers (e.g., ascorbic acid [19]) into the extravesicular space. In addition, hydrogel-forming solution as well as cross-linker and initiator can be microinjected directly into the internal compartment of a giant unilamellar phospholipid vesicle (GUV) [17].…”

“…In the course of this step, the required medium external to the lipobeads can be introduced. For example, lipobeads could be dispersed in distilled water [13,30,36], buffers with pH varied from 7.0 to 7.8 [1,8,9,11,14,16,17,[19][20][21]30], or aqueous solutions of sucrose [12,24,33,34]. If necessary, the prepared lipobeads can be dried by gentle evaporation in temperature gradient to be stored at 4°C.…”

Preparation of PVP hydrogel nanoparticles using lecithin vesicles

“…Polyacrylamide nanogels (from monomers) covered by phospholipids bilayers obtained by detergent depletion 35 or freeze-thaw cycles followed by extrusion 36 / sonication 11,17 presented diameters of 100 and 200 nm, respectively. Larger nanogels (about 450 nm) are obtained from encapsulation of 20% dextran hydroyethylmethacrylate solution ( -Mn= 19000) inside vesicles obtained by phospholipids film hydration, followed by extru- sion.…”