NOVEL BIOCOMPATIBLE CATIONIC COPOLYMERS BASED ON POLYASPARTHYLHYDRAZIDE BEING POTENT AS GENE VECTOR ON TUMOR CELLS

Gennara Cavallaro, Fabio Salvatore Palumbo, Gaetano Giammona, Arun K. Kotha, Nicole Tietze, Manfred Ogris, Ernst Wagner

Risultato della ricerca: Articlepeer review

6 Citazioni (Scopus)

Abstract

Introduction. The reaction between !,"-poly(aspartylhydrazide) (PAHy), a water soluble syntheticpolymer and 3-(carboxypropyl)trimethyl-ammonium chloride (CPTACl) produced copolymers bearingpermanent positive charges (PAHy–CPTA) with molecular weight of 10 kDa and PAHy–CPTAcopolymers differing in positive charge amount (18–58%) were chosen for biological investigations.Materials and methods. Biophysical properties of DNA/PAHy–CPTA polyplexes were evaluated interms of DNA condensation, zeta potential and size distribution. Cytotoxicity studies on Neuro2Amurine neuroblastoma cells evidenced absence of toxicity of these copolymers up to 300 2g/ml unlikelinear polyethylenimine (LPEI) that was highly toxic already at 20 2g/ml.Results and Discussion. PAHy–CPTA copolymers did not induce any erythrocyte aggregation up to1 mg/ml. Cellular interaction studies of PAHy–CPTA polyplexes evidenced a faster binding of thesepolyplexes 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 thetransfection efficiency of optimized LPEI polyplexes.Conclusions. Finally, in vivo application studies confirmed the biocompatibility of PAHy–CPTAcopolymers. With LPEI, clear signs of microvesicular fatty liver were observed and with LPEIpolyplexes significant weight loss. In strong contrast, PAHy–CPTA did not induce histopathologicalchanges or weight loss.
Lingua originaleEnglish
pagine (da-a)2213-2222
Numero di pagine10
RivistaPharmaceutical Research
Volume24 (12)
Stato di pubblicazionePublished - 2007

All Science Journal Classification (ASJC) codes

  • ???subjectarea.asjc.1300.1305???
  • ???subjectarea.asjc.1300.1313???
  • ???subjectarea.asjc.3000.3004???
  • ???subjectarea.asjc.3000.3003???
  • ???subjectarea.asjc.1600.1605???
  • ???subjectarea.asjc.2700.2736???

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