title: The influence of natural pulmonary surfactant on the efficacy of siRNA-loaded dextran nanogels.
abstract: OBJECTIVE
  Topical administration of siRNA nanocarriers is a promising approach in the treatment of pulmonary disorders. Pulmonary surfactant, covering the entire alveolar surface of mammalian lungs, will be one of the first interfaces that siRNA nanocarriers encounter upon inhalation therapy. Therefore, it is of outstanding importance to evaluate the impact of pulmonary surfactant on the performance of siRNA nanocarriers.
  
  
  METHODS
  The effect of natural lung-derived surfactants on the siRNA delivery capacity of dextran nanogels (DEX-NGs) was evaluated in vitro using flow cytometry and confocal microscopy.
  
  
  RESULTS
  Although the interaction with pulmonary surfactant decreases the cellular internalization of siRNA-loaded DEX-NGs significantly, the gene silencing potential of siRNA-loaded DEX-NGs was maintained. On the other hand, cationic lipid-based siRNA nanocarriers (Lipofectamine™ RNAiMAX) were incompatible with pulmonary surfactants.
  
  
  CONCLUSIONS
  Our data suggest that pulmonary surfactant can enhance the intracellular siRNA delivery by DEX-NGs, thereby possibly providing new therapeutic opportunities.
authors: Laboratory of General Biochemistry & Physical Pharmacy, Faculty of Pharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
authors: Lynn
authors: L
authors: De Backer
authors: Kevin
authors: K
authors: Braeckmans
authors: Jo
authors: J
authors: Demeester
authors: Stefaan C
authors: SC
authors: De Smedt
authors: Koen
authors: K
authors: Raemdonck
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002460:Cell Line; D003911:Dextrans / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D015316:Genetic Therapy; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000080385:Nanogels; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011094:Polyethyleneimine / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003911:Dextrans; D000080385:Nanogels; D011663:Pulmonary Surfactants; D034741:RNA, Small Interfering; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine