Polymerized (ethylene glycol) dimethacrylate–cholesteryl methacrylate liposomes: preparation and stability studies

Abstract

In this study, preparation of stable polymerized liposomes using monomeric mixture of poly(ethylene glycol) 400-dimethacrylate (PEG.DM) and cholesteryl methacrylate (ChMA) was carried out. Liposomes containing PEG.DM–ChMA monomers were prepared by a sonication method and subsequently polymerized using an ammonium persulfate/sodium metabisulfite redox system. Liposomes containing PEG.DM monomer was also prepared for comparative studies. Both monomeric and polymerized liposomes were characterized by Fourier transform (FT) IR, FT nuclear magnetic resonance (NMR) spectroscopy, transmission electron microscopy and turbidity measurement. The spectroscopic studies clearly confirmed the polymerization of ChMA and PEG.DM monomers in the liposomes. The transmission electron micrograph showed the spherical shape of both monomeric and polymerized liposomes. The average sizes of the PEG.DM and PEG.DM–ChMA containing monomeric liposomes are 420 nm and 400 nm, respectively, and the average sizes of the polymerized PEG.DM and PEG.DM–ChMA liposomes are 450 nm and 460 nm, respectively. The turbidity measurement indicated that both the polymerized liposomes are more stable than the monomeric liposomes. Vincristine sulfate (VCR), a water-soluble anticancer drug, was chosen as a model drug for incorporation in both the monomeric and polymerized liposomes. The percentage encapsulation was determined by completely breaking the liposome bilayers using Triton X-100. In vitro release of the encapsulated VCR from monomeric and polymerized liposomes were carried out in phosphate-buffered saline, pH 7.4 and in 1% (v/v) human plasma at 37°C. In both media, the polymerized liposomes released the drug in a sustained manner for prolonged period of time compared to the monomeric liposomes. Among the polymerized liposomes, the polymerized PEG.DM–ChMA liposomes released the drug for longer period of time than the polymerized PEG.DM liposomes. These results clearly suggested that the more stable polymerized PEG.DM–ChMA liposomes appear to be a better carrier for the delivery of therapeutic molecules.