title: Chitosan-thioglycolic acid conjugate: an alternative carrier for oral nonviral gene delivery?
abstract: Regarding safety concerns, nonviral gene delivery vehicles that have the required efficiency and safety for use in human gene therapy are being widely investigated. The aim of this study was to synthesize and evaluate a thiolated chitosan to improve the efficacy of oral gene delivery systems. Thiolated chitosan was synthesized by introducing thioglycolic acid (TGA) to chitosan via amide bond formation mediated by a carbodiimide. Based on this conjugate, nanoparticles with pDNA were generated at pH 4.0 and 5.0. Cytotoxicity of the thiolated chitosan/pDNA nanoparticles on Caco-2 cells was evaluated. The diameter of thiolated chitosan/pDNA nanoparticles was in the range of 100-200 nm. The zeta potential was determined to be 5-6 mV. Due to stability toward nucleases, the transfection rate of thiolated chitosan/pDNA nanoparticles was fivefold higher than that of unmodified chitosan/pDNA nanoparticles. Lactate dehydrogenase tests for thiolated chitosan/pDNA (pH 4.0 and 5.0) showed that (3.79 +/- 0.23)% and (2.9 +/- 0.13)% cell damage. According to these results, thiolated chitosan represents promising excipients for preparation DNA nanoparticles in nonviral gene delivery system.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innrain 52, 6020 Innsbruck, Austria.
authors.forename: Ronny
authors.initials: R
authors.lastname: Martien
authors.forename: Brigitta
authors.initials: B
authors.lastname: Loretz
authors.forename: Marlene
authors.initials: M
authors.lastname: Thaler
authors.forename: Sayeh
authors.initials: S
authors.lastname: Majzoob
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000284:Administration, Oral; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D018014:Gene Transfer Techniques; D006801:Humans; D008422:Materials Testing; D008854:Microscopy, Electron; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D012449:Safety; D013864:Thioglycolates / Q000737:chemistry*; D014162:Transfection
chemical_list: D004274:DNA, Recombinant; D004337:Drug Carriers; D013864:Thioglycolates; D048271:Chitosan