title: Hemocompatibility of siRNA loaded dextran nanogels.
abstract: Although the behavior of nanoscopic delivery systems in blood is an important parameter when contemplating their intravenous injection, this aspect is often poorly investigated when advancing from in vitro to in vivo experiments. In this paper, the behavior of siRNA loaded dextran nanogels in human plasma and blood is examined using fluorescence fluctuation spectroscopy, platelet aggregometry, flow cytometry and single particle tracking. Our results show that, in contrast to their negatively charged counterparts, positively charged siRNA loaded dextran nanogels cause platelet aggregation and show increased binding to human blood cells. Although PEGylating the nanogels did not have a significant effect on their interaction with blood cells, single particle tracking revealed that it is necessary to prevent their aggregation in human plasma. We therefore conclude that PEGylated negatively charged dextran nanogels are the most suited for further in vivo studies as they do not aggregate in human plasma and exhibit minimal interactions with blood cells.
authors: Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent, Belgium.
authors: Broes
authors: B
authors: Naeye
authors: Hendrik
authors: H
authors: Deschout
authors: Magnus
authors: M
authors: Röding
authors: Mats
authors: M
authors: Rudemo
authors: Joris
authors: J
authors: Delanghe
authors: Katrien
authors: K
authors: Devreese
authors: Jo
authors: J
authors: Demeester
authors: Kevin
authors: K
authors: Braeckmans
authors: Stefaan C
authors: SC
authors: De Smedt
authors: Koen
authors: K
authors: Raemdonck
mesh_terms: D001773:Blood Cells / Q000166:cytology / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008422:Materials Testing; D000080385:Nanogels; D010974:Platelet Aggregation; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D003911:Dextrans; D000080385:Nanogels; D034741:RNA, Small Interfering; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine