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2-diethylaminoethyl-dextran methyl methacrylate copolymer nonviral vector: still a long way toward the safety of aerosol gene therapy

Gene Therapy volume 20, pages 1022–1028 (2013)Cite this article

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Abstract

Revealing the lung tumor genome has directed the current treatment strategies toward targeted therapy. First line treatments targeting the genome of lung tumor cells have been approved and are on the market. However, they are limited by the small number of patients with the current investigated genetic mutations. Novel treatment administration modalities have been also investigated in an effort to increase the local drug deposition and disease control. In the current study, we investigated the safety of the new nonviral vector 2-diethylaminoethyl-dextran methyl methacrylate copolymer (DDMC; Ryujyu Science), which belongs to the 2-diethylaminoethyl-dextran family by aerosol administration. Thirty male BALBC mice, 2 month old, were included and divided into three groups. However, pathological findings indicated severe emphysema within three aerosol sessions. In addition, the CytoViva technique was applied for the first time to display the nonviral particles within the pulmonary tissue and emphysema lesions, and a spectral library of the nonviral vector was also established. Although our results in BALBC mice prevented us from further investigation of the DDMC nonviral vector as a vehicle for gene therapy, further investigation in animals with larger airways is warranted to properly evaluate the safety of the vector.

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Acknowledgements

We thank the Director of the experimental animal laboratory of ‘Theiagenio’ Anticancer Hospital; Frideriki Patakiouta for her support by using the installations of the laboratory. We also thank the Associate Professor of the Technical Institute of Aristotle University of Thessaloniki; Dr Paul Zarogoulidis thanks the Assistant Professor Chris Ritzoulis, Technical Institute of Food Administration, Aristotle University of Thessaloniki, Greece for his technical assistance in measuring the aerosol droplets with the Mastesizer 2000 laser scattering apparatus (Malvern). In addition, he thanks Jane F Century Chief Operating Officer, Penn-Century, Inc. http://www.penncentury.com for providing her technical expertise and material in order for this effort to be completed and presented. Finally, we thank the veterinarians; Kyriaki Papadimitriou and Froso Papagianni for the supervision of the animals throughout the project.

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Authors and Affiliations

  1. Pulmonary Department-Oncology Unit, ‘G. Papanikolaou’ General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

    P Zarogoulidis & K Zarogoulidis

  2. Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany

    P Zarogoulidis, K Darwiche & L Freitag

  3. II Medical Clinic, Coburg Hospital, University of Wuerzburg, Coburg, Germany

    W Hohenforst-Schmidt

  4. CytoViva Inc., Auburn, AL, USA

    L Krauss

  5. Experimental Animal Laboratory, ‘Theiageneio’ Anticancer Hospital, Thessaloniki, Greece

    D Sparopoulou

  6. Department of Pathology, ‘G. Papanikolaou’ General Hospital, Thessaloniki, Greece

    L Sakkas

  7. Department of Pathology, Clinic of Amberg, Amberg, Germany

    A Gschwendtner

  8. Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, China

    H Huang

  9. Pulmonary Department, Clinical Research, Nevada Cancer Center, Las Vegas, NV, USA

    F J Turner

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  1. P Zarogoulidis
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Zarogoulidis, P., Hohenforst-Schmidt, W., Darwiche, K. et al. 2-diethylaminoethyl-dextran methyl methacrylate copolymer nonviral vector: still a long way toward the safety of aerosol gene therapy. Gene Ther 20, 1022–1028 (2013). https://doi.org/10.1038/gt.2013.27

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