Pegylated GL67 lipoplexes retain their gene transfection activity after exposure to components of CF mucus.
The highly viscous secretions lining the upper airways and bronchi of cystic fibrosis (CF) patients may pose a significant barrier to successful gene therapy of the lung. In this report we examined the influence of CF mucus components (albumin, DNA, mucin and phospholipids) on the gene transfection activity of cationic DOTAP-based lipoplexes and pegylated GL67-based lipoplexes which previously have been used in CF clinical studies. Upon exposure of the cationic DOTAP:DOPE lipoplexes to either albumin, linear DNA or mucin (at concentration ratios expected to occur in vivo) a significant decrease in gene transfection activity was observed. This was primarily due to aggregation of the lipoplexes. However, exposure of pegylated GL67 lipoplexes to the same components did not affect their gene transfection activity. Indeed, it was determined that CF mucus components did not interact significantly with these pegylated GL67 lipoplexes. These results suggest that charge shielding of cationic gene carriers with pEG may favor their physicochemical stability in CF mucus and thereby aid in preserving their transfection activity.
Sanders
N N
NN
Faculty of Pharmacy, Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Ghent, Belgium.
De Smedt
S C
SC
Cheng
S H
SH
Demeester
J
J
D000418:Albumins / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000378:metabolism / Q000628:therapy*; D004247:DNA / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids; D008081:Liposomes / Q000378:metabolism*; D009077:Mucins / Q000494:pharmacology; D009093:Mucus / Q000378:metabolism*; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011092:Polyethylene Glycols / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism; D000644:Quaternary Ammonium Compounds; D014162:Transfection / Q000379:methods*; D016896:Treatment Outcome
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D000418:Albumins; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; D008081:Liposomes; D009077:Mucins; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011663:Pulmonary Surfactants; D000644:Quaternary Ammonium Compounds; C078272:SF-RI 1, bovine surfactant preparation; D011092:Polyethylene Glycols; D004247:DNA; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane