Hemocompatibility assessment of poly(2-dimethylamino ethylmethacrylate) (PDMAEMA)-based polymers

Abstract

Poly(2-dimethylamino-ethylmethacrylate) (PDMAEMA), a cationic polymer, has been widely reported as a nonviral carrier. Despite the fact that the cytotoxicity of this polymer has been extensively studied, there is a lack of information about its blood compatibility. Hence, this work evaluates the hemocompatibility of free-form PDMAEMA homopolymers differing in molecular weight (Mw) with or without a poly(ethylene glycol) (PEG) sequence in the form of a palm tree-like structure. Poly(ethylenimine) (PEI) was used as a reference in order to compare its hemoreactivity. Hemagglutination, hemolysis, platelet number, blood coagulation, and the complement systems were assessed in normal human whole blood according to the ISO 10993-4. Results showed that Mw, concentration, and incubation time strongly affected the hemocompatibility of the polymers evaluated. Our in vitro observations highlight that PDMAEMA homopolymers interacted strongly with the surface of the red blood cells but not with the inner structure of the membrane, while PEI behaved in the opposite way. No clear correlation has been evidenced between PDMAEMA-induced hemagglutination, PEI-induced hemagglutination, and hemolysis. Interestingly, if these polyelectrolytes strongly affect the platelets and blood coagulation cascades in a dose dependent way, none of them significantly affects the complement system. Our work reveals new knowledge on the toxicology of 2 families of polycations largely explored for gene delivery and on their mechanisms of cellular and humoral interactions.

Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin

“…Hemolysis assay in vitro was employed to evaluate toxicity of LDMP copolymer (Cerda-Cristerna et al, 2011;Meng et al, 2011). Heparinized rat erythrocytes were separated from rat blood by centrifugation at 3000 r/min for 30 min in a centrifuge and eluted using physiological saline to achromatic color for supernatant solution.…”

Stealth Nanogels of Histinylated Poly Ethyleneimine for Sustained Delivery of Methotrexate in Collagen-Induced Arthritis Model

“…To assay erythrocyte aggregation, samples were immediately imaged following incubation with the polymer solutions using an inverted-light microscope (Optika, Italy) at 200× magnification. The images were scored for the size of erythrocyte aggregates as previously described (24).…”

Cyto/hemocompatible magnetic hybrid nanoparticles (Ag2S–Fe3O4) with luminescence in the near-infrared region as promising theranostic materials

“…Compared to the animal cell toxicity assays, reactivity of blood is definitely more sensitive, taking into account that blood biological cascades can be activated by chemical groups residing on the surface of the nanomaterial. Although there are very few reports, both Ag 2 S and SPION are reported as hemocompatible materials, in general [37][38][39]. Therefore, hemolysis, morphology of blood cells, complement activation (C3a), and coagulation activation were studied for the evaluation of hemocompatibility of the nanoparticles.…”