title: Physicochemical and biological evaluation of cationic polymethacrylates as vectors for gene delivery.
abstract: We report here the physicochemical and biological evaluation of a series of polymethacrylates with side groups of different pK(a) values, such as tertiary amines, pyridine groups, acid functions and imidazole groups as synthetic vectors for gene delivery. The ability of the different polymers to condense DNA was studied by ethidium bromide exclusion tests and agarose gel electrophoresis. The results show that all polymers are able to condense DNA. Both the molecular weight and the chemical composition of the polymers have an influence on the DNA condensation process. Furthermore, the biological properties of the polymer-DNA complexes were investigated, including their haemolytic activity, cytotoxicity and in vitro transfection efficiency. Complexes based on polymers containing only tertiary amines, have a transfection efficiency similar to that of poly(ethyleneimine) (PEI). Polymers containing pyridine groups have a reduced transfection efficiency compared to polymers containing tertiary amines. Introduction of imidazole groups or acid functions results in a loss of the transfection efficiency of the corresponding complexes with DNA. In general, the viability of cells incubated with complexes based on the polymethacrylates is higher than with PEI. Polymers with high transfection efficiency induce erythrocyte lysis.
authors.affiliation: Polymer Materials Research Group, Department of Organic Chemistry, Ghent University, Ghent, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Dubruel
authors.forename: Bart
authors.initials: B
authors.lastname: Christiaens
authors.forename: Berlinda
authors.initials: B
authors.lastname: Vanloo
authors.forename: Ken
authors.initials: K
authors.lastname: Bracke
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Rosseneu
authors.forename: Joël
authors.initials: J
authors.lastname: Vandekerckhove
authors.forename: Etienne
authors.initials: E
authors.lastname: Schacht
mesh_terms: D000818:Animals; D019556:COS Cells; D002412:Cations; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002522:Chlorocebus aethiops; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000138:chemical synthesis*; D006461:Hemolysis / Q000187:drug effects / Q000502:physiology; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000737:chemistry; D014162:Transfection / Q000379:methods* / Q000639:trends
chemical_list: D002412:Cations; D011109:Polymethacrylic Acids