title: Biologically active bisquaternary ammonium chlorides: physico-chemical properties of long chain amphiphiles and their evaluation as non-viral vectors for gene delivery.
abstract: The biological properties of bisquaternary ammonium salts, which are derivatives of N,N-bisdimethyl-1,2-ethanediamine (bis-C(n)BEC), of general formula /C(n)H(2n+1)OOCCH2(CH3)2N(+)CH2CH2N(+)(CH3)2CH2COOC(n)H(2n+1)/2Cl-, were investigated (n=10, 12, 14). The interaction with model membrane was studied by differential scanning calorimetry experiments, and the apparent adiabatic molar compressibility of their solution as a function of concentration was obtained by sound velocity measurements. Their biological activities were assayed by Electrophoresis Mobility Shift, MTT proliferation, and transient transfection. All the investigated compounds interact with the DNA and are able to transfect DNA, when they are co-formulated with DOPE, with an efficiency significantly greater than that of a standard commercial transfection reagent. Bis-C(14)BEC is the only molecule able to deliver DNA inside the cells without a helper lipid, as shown by EGFP expression, albeit with a low efficiency in comparison with a standard commercial transfection reagent. This may be due to a slightly different interaction of bis-C14BEC from bis-C10BEC and bis-C12BEC with phospholipid bilayers. Bis-C10BEC and bis-C12BEC show a slight fluidizing effect, while bis-C14BEC increases stability of both the gel and the rippled gel phases.
authors.affiliation: Dipartimento di Scienze Farmacologiche, Biologiche e Chimiche Applicate, Università di Parma, Parco Area delle Scienze, 27A-43100 Parma, Italy. emilia.fisicaro@unipr.it
authors.forename: Emilia
authors.initials: E
authors.lastname: Fisicaro
authors.forename: Carlotta
authors.initials: C
authors.lastname: Compari
authors.forename: Elenia
authors.initials: E
authors.lastname: Duce
authors.forename: Gaetano
authors.initials: G
authors.lastname: Donofrio
authors.forename: Bozenna
authors.initials: B
authors.lastname: Rózycka-Roszak
authors.forename: Edyta
authors.initials: E
authors.lastname: Woźniak
mesh_terms: D000643:Ammonium Chloride / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D018014:Gene Transfer Techniques; D007700:Kinetics; D012996:Solutions; D013314:Stress, Mechanical
chemical_list: D012996:Solutions; D000643:Ammonium Chloride