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Polycations based on polyasparthylhydrazide for gene therapy

Gennara Cavallaro 1Manfred Ogris 2Fabio S. Palumbo Gaetano Giammona 

1. Università di Palermo (UNIPA), Viale delle Scienze, Pallermo 90128, Italy
2. Ludwig Maximilians Universitaet, Department of Pharmacy (LMU), Butenandtstr. 5-13, Munich 81377, Germany

Abstract


Hydrophilic polycations can be potentially useful for systemic gene delivery since their ability to form polyplexes with nucleic acids. α, β-poly(asparthylhydrazide) (PAHy), a water soluble synthetic macromolecule, was functionalized by using EDCI chemistry with 3-(carboxypropyl)trimethyl-ammonium chloride (CPTA) obtaining PAHy-CPTA copolymers. The derivatization degree (DD% mol/mol) of polycationic derivatives were detected by 1H-NMR and their main physico-chemical properties by SEC analysis. Previous chemical reactivity studies of naked PAHy evidenced the influence of condition reactions on molecular weight and degree of derivatization (DD% mol/mol) of obtained polycations. The capability of four different PAHy-CPTA derivatives (DD % mol/mol ranging from 18 to 58 % mol/mol) to complex plasmid DNA coding for luciferase and to transfect tumor cells at different plasmid to polycation ratios were performed using as positive control PEI polyplexes. In vitro transfection results evidenced that PAHy-CPTA copolymers having 48 and 58 % mol/mol show a high efficiency of transfection at DNA/polycation weight ratios 4.

 

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Presentation: oral at E-MRS Fall Meeting 2004, Symposium B, by Gennara Cavallaro
See On-line Journal of E-MRS Fall Meeting 2004

Submitted: 2004-05-19 23:54
Revised:   2009-06-08 12:55