Maqola

Role of Biophysical Parameters on ex Vivo and in Vivo Gene Transfer to the Airway Epithelium by Polyethylenimine/Albumin Complexes

Sante Di GioiaInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, MangiagalliJoanna RejmanInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, MangiagalliSalvatore CarrabinoInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, MangiagalliIda De FinoInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, MangiagalliCarsten RudolphInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, MangiagalliAnn DohertyInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, MangiagalliLaura HyndmanInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, MangiagalliMaurizio Di CiccoInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, MangiagalliElena CopreniInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, MangiagalliAlessandra BragonziInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, MangiagalliCarla ColomboInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, MangiagalliAlan BoydInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, MangiagalliMassimo ConeseInstitute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy, Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany, Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Free University of Berlin, Berlin, Germany, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh, U.K., Dipartimento di Otorinolaringoiatra, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli

2008en

ABI

Annotatsiya

Efficient gene transfer to the airways by nonviral vectors is a function of different parameters, among which the size and the charge of the transfecting particles. The aim of this study was to determine the transfection efficiency of polyethylenimine (PEI)/albumin polyplexes in ex vivo and in vivo models of respiratory epithelium and to correlate it with biophysical characteristics of the particles. Complexes were obtained by adding different amounts of human serum albumin (HSA) to PEI polyplexes preformed in saline. The presence of HSA caused the formation of bigger and more negative polyplexes and increased PEI transfection efficiency in primary respiratory epithelial cells by 4-6-fold. For in vivo administration to the lung, PEI polyplexes were formed in water and optimized with respect to the N/ P ratio. PEI/pC-Luc complexes gave the highest luciferase expression at N/ P 15 when administered through the trachea. At this N/ P ratio, the size and the surface charge of albumin-containing polyplexes were not different as compared with plain PEI polyplexes. Formulation of PEI polyplexes in the presence of HSA or murine serum albumin (MSA) resulted in a 2-fold increase in luciferase expression. In mice treated with PEI or PEI/MSA polyplexes containing the nuclear beta-gal gene, X-gal staining revealed that transfected cells localized at the bronchiolar epithelium and that PEI/MSA transfected four times as many cells as PEI ( p < 0.05). Finally, double administration of PEI/MSA polyplexes resulted in a further enhancement of transfection of the lung. Our data show that serum albumin enhances PEI-mediated gene transfer to airway epithelial cells in vivo, likely facilitating the uptake of polyplexes, and indicate that this formulation would fulfill the requirement of repeated administration, as necessary in chronic lung diseases like cystic fibrosis.

Hali tarjima qilinmagan

Identifikatorlar

DOI: 10.1021/bm701190p

Iqtiboslar va manbalar

2 ta iqtibos0 ta foydalanilgan manba

Koʻrsatkichlar — AkademScholar