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

Joris P. Schillemans, Frits M. Flesch, Wim E. Hennink, and Cornelus F. van Nostrum*

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS),
Utrecht UniVersity, P.O. Box 80.082, 3508 TB Utrecht, The Netherlands


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.