title: Studies towards biocompatibility of PAMAM dendrimers--overall hemostasis potential and integrity of the human aortic endothelial barrier.
abstract: The last decade has brought many examples of utilization of dendrimers as drug delivery systems; however, their possible application is limited because of inherent toxicity associated with them. This study discusses the influence of G1-G4 PAMAM-NH2 dendrimers on the process of hemostasis and integrity of endothelial monolayer. The global assay of coagulation and fibrinolysis was investigated spectrophotometrically by means of CL-test at 405 nm. Thrombin (0.5 I U/mL) and t-PA (240 ng/mL) were used to obtain clotting and lysis curve. The activity of thrombin was determined by means of chromogenic substrate S-2238. The influence of PAMAM dendrimers on the barrier properties of human primary aortal endothelium was assessed by means of method based on the measurements of the impedance changes of the cells. Observed multidirectional impact of dendrimers, without affecting the thrombin activity, on clot formation, its stabilization and fibrinolysis could be regarded as important when trying to use them clinically. It is crucial that examined PAMAM dendrimers did not lead to spontaneous aggregation of fibrinogen. Importantly, examined polymers have concentration- and generation-dependent adverse effect towards the endothelial monolayer.
  
  
  RESULTS
  of described studies provide additional insight into PAMAM dendrimers toxicity associated with systemic administration and underscore the necessity for further research.
authors.affiliation: Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland. Electronic address: magdalena.markowicz@umed.lodz.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Markowicz-Piasecka
authors.affiliation: Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1/5, 91-347 Lodz, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Łuczak
authors.affiliation: Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1/5, 91-347 Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Chałubiński
authors.affiliation: Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1/5, 91-347 Lodz, Poland.
authors.forename: Marlena
authors.initials: M
authors.lastname: Broncel
authors.affiliation: Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Mikiciuk-Olasik
authors.affiliation: Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Sikora
mesh_terms: D001011:Aorta / Q000166:cytology; D001777:Blood Coagulation / Q000187:drug effects*; D002478:Cells, Cultured; D050091:Dendrimers / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006487:Hemostasis; D006801:Humans; D013917:Thrombin / Q000378:metabolism
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D013917:Thrombin
keywords: Clot formation; Coagulation; Endothelium; Fibrinolysis; Nanotechnology; PAMAM dendrimers