Kinetic analysis of nanoparticulate polyelectrolyte complex interactions with endothelial cells.
A non-toxic, nanoparticulate polyelectrolyte complex (PEC) drug delivery system was formulated to maintain suitable physicochemical properties at physiological pH. Toxicity, binding, and internalization were evaluated in relevant microvascular endothelial cells. PEC were non-toxic, as indicated by cell proliferation studies and propidium iodide staining. Inhibitor studies revealed that PEC were bound, in part, via heparan sulfate proteoglycans and internalized through macropinocytosis. A novel, flow cytometric, Scatchard protocol was established and showed that PEC, in the absence of surface modification, bind cells non-specifically with positive cooperativity, as seen by graphical transformations.
Hartig
Sean M
SM
Department of Chemical Engineering, Vanderbilt University, Nashville, TN 37235-1604, USA.
Greene
Rachel R
RR
Carlesso
Gianluca
G
Higginbotham
James N
JN
Khan
Wasif N
WN
Prokop
Ales
A
Davidson
Jeffrey M
JM
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004573:Electrolytes / Q000493:pharmacokinetics* / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008657:Metabolic Clearance Rate; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*
D004337:Drug Carriers; D004573:Electrolytes