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Preparation and characterization of chitosan and trimethyl-chitosanmodified poly-(ε-caprolactone) nanoparticles as DNA carriers

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Abstract

The purpose of this research was to prepare poly-(ε-caprolactone) (PCL) particles by an emulsion-diffusion-evaporation method using a blend of poly-(vinyl alcohol) and chitosan derivatives as stabilizers. The chitosan derivatives used were chitosan hydrochloride and trimethyl chitosans (TMC) with varying degrees of quaternization. Particle characteristics-size, zeta potential, surface morphology, cytotoxicity, and transfection efficiency-were investigated. The developed method yields PCL nanoparticles in the size range of 250 to 300 nm with a positive surface charge (2.5 to 6.8 mV). The cytotoxicity was found to be moderate and virtually independent of the stabilizers' concentration with the exception of the highly quaternized TMC (degree of substitution 66%) being significantly more toxic. In immobilization experiments with gel electrophoresis, it could be shown that these cationic nanoparticles (NP) form stable complexes with DNA at a NP:DNA ratio of 3:1. These nanoplexes showed a significantly higher transfection efficiency on COS-1 cells than naked DNA.

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Authors and Affiliations

  1. Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Building 8.1, 66123, Saarbrücken, Germany

    Jochen Haas & Claus-Michael Lehr

  2. Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research, SAS Nagar, 160 062, Punjab, India

    M. N. V Ravi Kumar

  3. Division of Pharmaceutical Technology, LACDR, Leiden University, 2300 RA, Leiden, The Netherlands

    Gerrit Borchard

  4. Department of Pharmaceutical Technology and Biopharmacy, Philipps University of Marburg, 35032, Marburg, Germany

    Udo Bakowsky

Authors
  1. Jochen Haas
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  2. M. N. V Ravi Kumar
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  3. Gerrit Borchard
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  4. Udo Bakowsky
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  5. Claus-Michael Lehr
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Correspondence to Claus-Michael Lehr.

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Published: August 10, 2005

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Haas, J., Ravi Kumar, M.N.V., Borchard, G. et al. Preparation and characterization of chitosan and trimethyl-chitosanmodified poly-(ε-caprolactone) nanoparticles as DNA carriers. AAPS PharmSciTech 6, 6 (2005). https://doi.org/10.1208/pt060106

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  • DOI: https://doi.org/10.1208/pt060106

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