title: 2-diethylaminoethyl-dextran methyl methacrylate copolymer nonviral vector: still a long way toward the safety of aerosol gene therapy.
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.
authors.affiliation: 1] Pulmonary Department-Oncology Unit, 'G. Papanikolaou' General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece [2] Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Zarogoulidis
authors.forename: W
authors.initials: W
authors.lastname: Hohenforst-Schmidt
authors.forename: K
authors.initials: K
authors.lastname: Darwiche
authors.forename: L
authors.initials: L
authors.lastname: Krauss
authors.forename: D
authors.initials: D
authors.lastname: Sparopoulou
authors.forename: L
authors.initials: L
authors.lastname: Sakkas
authors.forename: A
authors.initials: A
authors.lastname: Gschwendtner
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.forename: F J
authors.initials: FJ
authors.lastname: Turner
authors.forename: L
authors.initials: L
authors.lastname: Freitag
authors.forename: K
authors.initials: K
authors.lastname: Zarogoulidis
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D003637:DEAE-Dextran / Q000008:administration & dosage / Q000633:toxicity*; D004646:Emphysema / Q000139:chemically induced*; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000628:therapy; D008297:Male; D020366:Methylmethacrylate / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D011897:Random Allocation
chemical_list: D020366:Methylmethacrylate; D003637:DEAE-Dextran