Extracellular barriers in respiratory gene therapy

被引:182
作者
Sanders, Niek [1 ,2 ]
Rudolph, Carsten [3 ,4 ]
Braeckmans, Kevin [2 ]
De Smedt, Stefaan C. [2 ]
Demeester, Joseph [2 ]
机构
[1] Univ Ghent, Fac Vet Med, Dept Nutr Genet & Ethol, Lab Gene Therapy, B-9820 Merelbeke, Belgium
[2] Univ Ghent, Fac Pharm, Gen Biochem & Phys Pharm Labs, B-9000 Ghent, Belgium
[3] Univ Munich, Dept Pediat, D-80337 Munich, Germany
[4] Free Univ Berlin, Dept Pharm, D-14166 Berlin, Germany
关键词
Respiratory gene therapy; NANs; Nucleic acid containing nanoparticles; Mucus Alveolar fluid; CYSTIC-FIBROSIS SPUTUM; BRONCHOALVEOLAR LAVAGE FLUID; POLYMER-COATED ADENOVIRUS; IN-VITRO; AIRWAY EPITHELIUM; PULMONARY SURFACTANT; DNA DELIVERY; MUCOLYTIC AGENTS; MAGNETIC FORCE; MUC5B MUCINS;
D O I
10.1016/j.addr.2008.09.011
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Respiratory gene therapy has been considered for the treatment of a broad range of pulmonary disorders. However, respiratory secretions form an important barrier towards the pulmonary delivery of therapeutic nucleic acids. In this review we will start with a brief description of the biophysical properties of respiratory mucus and alveolar fluid. This must allow the reader to gain insights into the mechanisms by which respiratory secretions may impede the gene transfer efficiency of nucleic acid containing nanoparticles (NANs). Subsequently, we will summarize the efforts that have been done to understand the barrier properties of respiratory mucus and alveolar fluid towards the respiratory delivery of therapeutic nucleic acids. Finally, new and current strategies that can overcome the inhibitory effects of respiratory secretions are discussed. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:115 / 127
页数:13
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