title: Effect of PEGylation on the diffusion and stability of chitosan-DNA polyplexes in collagen gels.
abstract: Diffusion through the extracellular matrix (ECM) is a critical step for the delivery of nanoparticles and genes. Gene delivery requires a carrier that protects the nucleic acid from degradation and facilitates transport. Chitosan is a promising carrier. To increase the circulation time, PEGylation of the carrier is performed. However, the effect of PEGylation on the transport and stability of gene delivery systems in the ECM has only been studied in solutions containing ECM components. We used polymerized collagen and collagen-hyaluronic acid (HA) gels to study the effects of PEGylation on the diffusion and stability of chitosan-DNA polyplexes. We found that PEGylation of the polyplexes was required for diffusion to occur, and PEGylation increased the dissociation between DNA and chitosan to some extent. The presence of HA had a contradictory role: it decreased the penetration depth of PEGylated polyplexes into the gels and increased the diffusion of the polyplexes being mixed into the gels.
authors.affiliation: Department of Physics, The Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lélu
authors.forename: Sabina P
authors.initials: SP
authors.lastname: Strand
authors.forename: Jan
authors.initials: J
authors.lastname: Steine
authors.forename: Catharina de Lange
authors.initials: Cde L
authors.lastname: Davies
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D048271:Chitosan / Q000737:chemistry / Q000378:metabolism; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004058:Diffusion / Q000187:drug effects; D004355:Drug Stability; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000032:analysis; D005782:Gels / Q000737:chemistry* / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism; D018613:Microscopy, Confocal; D053758:Nanoparticles; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013194:Staining and Labeling
chemical_list: D001672:Biocompatible Materials; D005782:Gels; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid; D003094:Collagen; D004247:DNA; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate