title: Comparative cellular pharmacokinetics and pharmacodynamics of siRNA delivery by SPANosomes and by cationic liposomes.
abstract: Mechanistic understanding of intracellular trafficking is important for the development of small interfering RNA (siRNA) delivery vehicles. Here, we describe a novel methodology to quantitatively analyze nanocarrier-mediated disposition of siRNA. Cellular uptake and cytoplasmic release of siRNA over time were quantified by measuring the fluorescence intensities of fluorescently-labeled siRNAs and molecular beacons using flow cytometry. This method was used to investigate the cellular pharmacokinetics (PK) of siRNA delivery by SPANosomes (SP) and by cationic liposomes (CL). The results showed that the superior pharmacodynamic (PD) response of SP was because it enhanced transport of siRNA into the cytoplasm compared to the CL. The divergent cellular pharmacokinetic profiles of the two formulations were associated with different cellular entry pathways. These findings can facilitate the rational design of more efficient siRNA delivery vehicles in the future.
  
  
  BACKGROUND
  In this paper the authors describe a novel methodology to quantitatively analyze nanocarrier-mediated disposition of small interfering RNA, comparing SPANosomes with cationic liposomes as delivery systems with different entry pathways.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Zhou
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.forename: Mitch A
authors.initials: MA
authors.lastname: Phelps
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
mesh_terms: D019540:Area Under Curve; D001483:Base Sequence; D002412:Cations; D002460:Cell Line; D017931:DNA Primers; D020868:Gene Silencing; D006801:Humans; D008081:Liposomes; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D002412:Cations; D017931:DNA Primers; D008081:Liposomes; D034741:RNA, Small Interfering