title: How do the full-generation poly(amido)amine (PAMAM) dendrimers activate blood platelets? Activation of circulating platelets and formation of "fibrinogen aggregates" in the presence of polycations.
abstract: Direct use of poly(amido)amine (PAMAM) dendrimers as drugs may be limited, due to uncertain (cyto)toxicity. Peripheral blood components, which constitute the first line of a contact with administered pharmaceuticals, may become vastly affected by PAMAM dendrimers. The aim of this study was to explore how PAMAMs' polycationicity might affect blood platelet activation and reactivity, and thus trigger various haemostatic events. We monitored blood platelet reactivity in rats with experimental diabetes upon a long-term administration of the unmodified PAMAM dendrimers. In parallel, the effects on blood flow in a systemic circulation was recorded intravitally in mice administered with PAMAM G2, G3 or G4. Compounding was the in vitro approach to monitor the impact of PAMAM dendrimers on blood platelet activation and reactivity and on selected haemostatic and protein conformation parameters. We demonstrated the activating effects of polycations on blood platelets. Some diversity of the revealed outcomes considerably depended on the used approach and the particular technique employed to monitor blood platelet function. We discovered undesirable impact of plain PAMAM dendrimers on primary haemostasis and their prothrombotic influence. We emphasize the need of a more profound verifying of all the promising findings collected for PAMAMs with the use of well-designed in vivo preclinical studies.
authors: Department of Haemostasis and Haemostatic Disorders, Chair of Biomedical Sciences, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland. Electronic address: cezary.watala@umed.lodz.pl.
authors: Cezary
authors: C
authors: Watala
authors: Department of Haemostasis and Haemostatic Disorders, Chair of Biomedical Sciences, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
authors: Kamil
authors: K
authors: Karolczak
authors: Department of Haemostasis and Haemostatic Disorders, Chair of Biomedical Sciences, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
authors: Hassan
authors: H
authors: Kassassir
authors: Department of Haemostasis and Haemostatic Disorders, Chair of Biomedical Sciences, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
authors: Marcin
authors: M
authors: Talar
authors: Department of Haemostasis and Haemostatic Disorders, Chair of Biomedical Sciences, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
authors: Tomasz
authors: T
authors: Przygodzki
authors: Department of Haemostasis and Haemostatic Disorders, Chair of Biomedical Sciences, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
authors: Katarzyna
authors: K
authors: Maczynska
authors: University of Lodz, Faculty of Biology and Environmental Protection, Department of Thermobiology, Pomorska 141/143, 90-236 Lodz, Poland.
authors: Magdalena
authors: M
authors: Labieniec-Watala
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D003094:Collagen / Q000494:pharmacology; D050091:Dendrimers / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D015539:Platelet Activation / Q000187:drug effects; D011107:Polylysine / Q000494:pharmacology; D011113:Polymyxins / Q000494:pharmacology; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000187:drug effects
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D011113:Polymyxins; D011107:Polylysine; D016718:Arachidonic Acid; D005340:Fibrinogen; D003094:Collagen
keywords: Blood platelets; Full-generation PAMAM dendrimers; In vivo animal models; Laser Doppler flowmetry; Primary haemostasis