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Novel Biocompatible Cationic Copolymers Based on Polyaspartylhydrazide Being Potent as Gene Vector on Tumor Cells

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Novel Biocompatible Cationic Copolymers Based on Polyaspartylhydrazide Being Potent as Gene Vector on Tumor Cells

Auteurs : Manfred Ogris [Allemagne] ; Arun K. Kotha [Allemagne] ; Nicole Tietze [Allemagne] ; Ernst Wagner [Allemagne] ; Fabio Salvatore Palumbo [Italie] ; Gaetano Giammona [Italie] ; Gennara Cavallaro [Italie]

Source :

Pharmaceutical Research [ 0724-8741 ] ; 2007-12-01.

RBID : ISTEX:1B7BC7B3F26278B757C57C2D43F196E395A3CFD7

English descriptors

KwdEn :
- cytotoxicity, liver toxicity, nonviral gene delivery, transfection.

Abstract

Abstract: Introduction: The reaction between α,β-poly(aspartylhydrazide) (PAHy), a water soluble synthetic polymer and 3-(carboxypropyl)trimethyl-ammonium chloride (CPTACl) produced copolymers bearing permanent positive charges (PAHy–CPTA) with molecular weight of 10 kDa and PAHy–CPTA copolymers differing in positive charge amount (18–58%) were chosen for biological investigations. Materials and methods: Biophysical properties of DNA/PAHy–CPTA polyplexes were evaluated in terms of DNA condensation, zeta potential and size distribution. Cytotoxicity studies on Neuro2A murine neuroblastoma cells evidenced absence of toxicity of these copolymers up to 300 μg/ml unlike linear polyethylenimine (LPEI) that was highly toxic already at 20 μg/ml. Results and Discussion: PAHy–CPTA copolymers did not induce any erythrocyte aggregation up to 1 mg/ml. Cellular interaction studies of PAHy–CPTA polyplexes evidenced a faster binding of these polyplexes with cells compared to DNA/LPEI polyplexes. The in vitro transfection ability of PAHy–CPTA polyplexes was strongly affected by experimental conditions reaching about 10% of the transfection efficiency of optimized LPEI polyplexes. Conclusions: Finally, in vivo application studies confirmed the biocompatibility of PAHy–CPTA copolymers. With LPEI, clear signs of microvesicular fatty liver were observed and with LPEI polyplexes significant weight loss. In strong contrast, PAHy–CPTA did not induce histopathological changes or weight loss.

Url:

https://api.istex.fr/ark:/67375/VQC-S4D5GLD5-2/fulltext.pdf

DOI: 10.1007/s11095-007-9403-4

Affiliations:

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Le document en format XML

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<front><div type="abstract" xml:lang="en">Abstract: Introduction: The reaction between α,β-poly(aspartylhydrazide) (PAHy), a water soluble synthetic polymer and 3-(carboxypropyl)trimethyl-ammonium chloride (CPTACl) produced copolymers bearing permanent positive charges (PAHy–CPTA) with molecular weight of 10 kDa and PAHy–CPTA copolymers differing in positive charge amount (18–58%) were chosen for biological investigations. Materials and methods: Biophysical properties of DNA/PAHy–CPTA polyplexes were evaluated in terms of DNA condensation, zeta potential and size distribution. Cytotoxicity studies on Neuro2A murine neuroblastoma cells evidenced absence of toxicity of these copolymers up to 300 μg/ml unlike linear polyethylenimine (LPEI) that was highly toxic already at 20 μg/ml. Results and Discussion: PAHy–CPTA copolymers did not induce any erythrocyte aggregation up to 1 mg/ml. Cellular interaction studies of PAHy–CPTA polyplexes evidenced a faster binding of these polyplexes with cells compared to DNA/LPEI polyplexes. The in vitro transfection ability of PAHy–CPTA polyplexes was strongly affected by experimental conditions reaching about 10% of the transfection efficiency of optimized LPEI polyplexes. Conclusions: Finally, in vivo application studies confirmed the biocompatibility of PAHy–CPTA copolymers. With LPEI, clear signs of microvesicular fatty liver were observed and with LPEI polyplexes significant weight loss. In strong contrast, PAHy–CPTA did not induce histopathological changes or weight loss.</div>
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Novel Biocompatible Cationic Copolymers Based on Polyaspartylhydrazide Being Potent as Gene Vector on Tumor Cells

Novel Biocompatible Cationic Copolymers Based on Polyaspartylhydrazide Being Potent as Gene Vector on Tumor Cells

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Abstract

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