Aggregation behavior of cationic nanohydrogel particles in human blood serum.
For systemic siRNA delivery applications, well-defined drug carriers are required that guarantee stability for both carrier and cargo. Among various concepts progressing in market or final development, cationic nanohydrogel particles may serve as novel transport media especially designed for siRNA-in vivo experiments. In this work, the interaction of nanohydrogel particles with proteins and serum components was studied via dynamic light scattering in human blood serum as novel screening method prior to applications in vivo. The formation of larger aggregates mostly caused by charge interaction with albumin could be suppressed by nanogel loading with siRNA affording a neutral zeta potential for the complex. Preliminary in vivo studies confirmed the results inside the light-scattering cuvette. Although both carrier and cargo may have limited stability on their own under physiological relevant conditions, they can form safe and stable complexes at a charge neutralized ratio and thus making them applicable to systemic siRNA delivery.
Institute of Organic Chemistry, Johannes Gutenberg-University Mainz , Duesbergweg 10-14, D-55099 Mainz, Germany.
Lutz
L
Nuhn
Sabine
S
Gietzen
Kristin
K
Mohr
Karl
K
Fischer
Kazuko
K
Toh
Kanjiro
K
Miyata
Yu
Y
Matsumoto
Kazunori
K
Kataoka
Manfred
M
Schmidt
Rudolf
R
Zentel
D002412:Cations; D004337:Drug Carriers / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D020100:Hydrogels / Q000493:pharmacokinetics; D008027:Light; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011094:Polyethyleneimine / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D034741:RNA, Small Interfering; D012542:Scattering, Radiation; D044967:Serum / Q000378:metabolism
D002412:Cations; D004337:Drug Carriers; D020100:Hydrogels; D000080385:Nanogels; D034741:RNA, Small Interfering; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine