title: Physicochemical and biological evaluation of siRNA polyplexes based on PEGylated Poly(amido amine)s.
abstract: OBJECTIVE
  Use of RNA interference as novel therapeutic strategy is hampered by inefficient delivery of its mediator, siRNA, to target cells. Cationic polymers have been thoroughly investigated for this purpose but often display unfavorable characteristics for systemic administration, such as interactions with serum and/or toxicity.
  
  
  METHODS
  We report the synthesis of a new PEGylated polymer based on biodegradable poly(amido amine)s with disulfide linkages in the backbone. Various amounts of PEGylated polymers were mixed with their unPEGylated counterparts prior to polyplex formation to alter PEG content in the final complex.
  
  
  RESULTS
  PEGylation effectively decreased polyplex surface charge, salt- or serum-induced aggregation and interaction with erythrocytes. Increasing amount of PEG in formulation also reduced its stability against heparin displacement, cellular uptake and subsequent silencing efficiency. Yet, for polyplexes with high PEG content, significant gene silencing efficacy was found, which was combined with almost no toxicity.
  
  
  CONCLUSIONS
  PEGylated poly(amido amine)s are promising carriers for systemic siRNA delivery in vivo.
authors.affiliation: Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508, TB, Utrecht, The Netherlands. P.Vader@uu.nl
authors.forename: Pieter
authors.initials: P
authors.lastname: Vader
authors.forename: Leonardus J
authors.initials: LJ
authors.lastname: van der Aa
authors.forename: Johan F J
authors.initials: JF
authors.lastname: Engbersen
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Schiffelers
mesh_terms: D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D004912:Erythrocytes / Q000166:cytology; D006801:Humans; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics
chemical_list: C531249:Poly(amidoamine); D011073:Polyamines; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols