title: Preparation and characterization of chitosan and trimethyl-chitosan-modified poly-(epsilon-caprolactone) nanoparticles as DNA carriers.
abstract: The purpose of this research was to prepare poly-(epsilon-caprolactone) (PCL) particles by an emulsion-diffusion-evaporation method using a blend of poly-(vinyl alcohol) and chitosan derivatives as stabilizers. The chitosan derivatives used were chitosan hydrochloride and trimethyl chitosans (TMC) with varying degrees of quaternization. Particle characteristics-size, zeta potential, surface morphology, cytotoxicity, and transfection efficiency-were investigated. The developed method yields PCL nanoparticles in the size range of 250 to 300 nm with a positive surface charge (2.5 to 6.8 mV). The cytotoxicity was found to be moderate and virtually independent of the stabilizers' concentration with the exception of the highly quaternized TMC (degree of substitution 66%) being significantly more toxic. In immobilization experiments with gel electrophoresis, it could be shown that these cationic nanoparticles (NP) form stable complexes with DNA at a NP:DNA ratio of 3:1. These nanoplexes showed a significantly higher transfection efficiency on COS-1 cells than naked DNA.
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Building 8.1, 66123 Saarbrücken, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Haas
authors.forename: M N V
authors.initials: MN
authors.lastname: Ravi Kumar
authors.forename: Gerrit
authors.initials: G
authors.lastname: Borchard
authors.forename: Udo
authors.initials: U
authors.lastname: Bakowsky
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D000818:Animals; D019556:COS Cells; D002208:Caproates / Q000008:administration & dosage / Q000138:chemical synthesis*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D048271:Chitosan / Q000008:administration & dosage / Q000138:chemical synthesis*; D002522:Chlorocebus aethiops; D004247:DNA / Q000008:administration & dosage / Q000138:chemical synthesis*; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis*; D007783:Lactones / Q000008:administration & dosage / Q000138:chemical synthesis*; D049329:Nanostructures / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D002208:Caproates; D004337:Drug Carriers; D007783:Lactones; C121056:caprolactone; D004247:DNA; D048271:Chitosan