“…We and others have previously reported that platelet aggregation is a sensitive in vitro indicator of thrombogenicity [19]. Sterilization of all four nanoparticle samples by autoclave and all doses of gamma irradiation resulted in an up to five-fold increase in the tendency to cause platelet aggregation, at parts-per-thousand concentrations (Figure 4).…”
Silver nanoparticles are commonly used in a variety of commercial and medical products. Here we investigate the effects of standard sterilization methods, including heat/steam (autoclave) and gamma-irradiation on the structural integrity and biocompatibility of citrate-stabilized silver nanoparticles with nominal sizes of 20, 40, 60 and 80 nm. Particle size, shape and in vitro biocompatibility were studied pre- and post-sterilization. Sterilization by gamma irradiation at dose levels commonly used in medical device industry (15, 25 and 50 kGy) resulted in dramatic changes in particle size and morphology, as monitored by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Exposing the particles to a chemical producer of hydroxyl radicals (N-hydroxy-2-pyridinethione) allowed us to duplicate the sterilization-based changes in size and morphology, implying a free radical mechanism of action. Compared to untreated controls, we also observed a three- to five-fold increase in tendency of sterilized silver nanoparticles to cause platelet aggregation, a sensitive in vitro indicator of thrombogenicity.
“…We and others have previously reported that platelet aggregation is a sensitive in vitro indicator of thrombogenicity [19]. Sterilization of all four nanoparticle samples by autoclave and all doses of gamma irradiation resulted in an up to five-fold increase in the tendency to cause platelet aggregation, at parts-per-thousand concentrations (Figure 4).…”
Silver nanoparticles are commonly used in a variety of commercial and medical products. Here we investigate the effects of standard sterilization methods, including heat/steam (autoclave) and gamma-irradiation on the structural integrity and biocompatibility of citrate-stabilized silver nanoparticles with nominal sizes of 20, 40, 60 and 80 nm. Particle size, shape and in vitro biocompatibility were studied pre- and post-sterilization. Sterilization by gamma irradiation at dose levels commonly used in medical device industry (15, 25 and 50 kGy) resulted in dramatic changes in particle size and morphology, as monitored by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Exposing the particles to a chemical producer of hydroxyl radicals (N-hydroxy-2-pyridinethione) allowed us to duplicate the sterilization-based changes in size and morphology, implying a free radical mechanism of action. Compared to untreated controls, we also observed a three- to five-fold increase in tendency of sterilized silver nanoparticles to cause platelet aggregation, a sensitive in vitro indicator of thrombogenicity.
“…Little is known about the toxicity of NMs introduced into the bloodstream (Simak 2009). Interactions of foreign materials with blood and its elements constitute a key point of any biocompatibility studies (Dobrovolskaia et al 2008a, b;Simak 2009). Furthermore, standardised and validated protocols for testing NP biocompatibility are needed (Dobrovolskaia et al 2008b).…”
Section: Discussionmentioning
confidence: 99%
“…Platelet activation leads to the exposure of phosphatidylserine on the plasma membrane, forming a procoagulant surface for activation complexes of the plasma coagulation system. Platelet activation and aggregation results in the formation of primary haemostatic plug, which is enforced with fibrin network as a structural result of activation of the plasma coagulation system (Simak 2009). Besides their critical role in haemostasis, platelets play critical roles in other different processes (Smyth et al 2009).…”
Section: Introductionmentioning
confidence: 99%
“…Moreover, the type of exposure and the pharmacokinetic behaviour of each specific NM may critically impact the effects on platelets (Simak 2009). Experimentally, the impact on platelet function by foreign materials can be assessed by a wide range of techniques based on different principles (light transmission aggregometry (LTA), Platelet Function Analyze-100 Ò (PFA-100 Ò ), whole-blood impedance aggregometry, Cone-and-Plate(let) analyser (Impact-R Ò ) and electron microscopy).…”
Section: Introductionmentioning
confidence: 99%
“…Methods for platelet testing have been extensively reviewed elsewhere (Favaloro et al 2010;Harrison & Mumford 2009). Today, few studies have reported the potential interactions of NMs with the platelet function (Bihari et al 2010;Ferraz et al 2008;Geys et al 2008;Karagkiozaki et al 2010;Lacerda et al 2010;Miller & Senjen 2008;Radomski et al 2005;Semberova et al 2009;Shrivastava et al 2009;Simak 2009;Stevens et al 2009). Moreover, internal quality control and external quality assurance are in their infancy for platelet function testing despite the many years in which these tests have been performed within diagnostic haemostasis laboratories (Favaloro 2009).…”
The study of the haemocompatibility of nanomaterials that could be in contact with blood (e.g. nanoparticle (NP)-based drug-delivery system) is of major importance. The primary objective of this study was to compare the ability of six platelet functional tests to assess the impact of NPs on platelet function. The secondary objective was to determine an accurate and reliable screening test to measure the potential impact of NPs on primary haemostasis whatever their physicochemical properties. Four types of carbon NPs (carbon black, fullerenes, single-walled carbon nanotubes and multi-walled carbon nanotubes) were investigated on six platelet function tests: light transmission aggregometry, whole-blood impedance aggregometry, platelet function analyser-100 (PFA-100®) and Cone-and-Plate(let) analyser (Impact-R®), transmission- and field emission gun scanning electron microscopy (FEG-SEM). We considered that Impact-R® supported by FEG-SEM is the reference method to investigate the potential impact of NPs on platelet function.
Blood platelets are essential in maintaining hemostasis. Various materials can activate platelets and cause them to aggregate. Platelet aggregation in vitro is often used as a marker for materials’ thrombogenic properties and studying nanomaterial interaction with platelets is an important step toward understanding their hematocompatibility. Here we report evaluation of 12 formulations of PAMAM dendrimers varying in size and surface charge. Using a cell counter based method, light transmission aggregometry and scanning electron microscopy, we show that only large cationic dendrimers, but not anionic, neutral or small cationic dendrimers, induce aggregation of human platelets in plasma in vitro. The aggregation caused by large cationic dendrimers was proportional to the number of surface amines. The observed aggregation was not associated with membrane microparticle release, and was insensitive to a variety of chemical and biological inhibitors known to interfere with various pathways of platelet activation. Taken in context with previously reported studies, our data suggest that large cationic PAMAM dendrimers induce platelet aggregation through disruption of membrane integrity.
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