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Influence cationic and anionic PAMAM dendrimers of low generation on selected hemostatic parameters in vitro.
Aisina, Roza; Mukhametova, Liliya; Ivanova, Elizaveta.
Afiliação
  • Aisina R; Chemical Enzymology Department, Chemistry Faculty, Lomonosov Moscow State University, 119991 Moscow, Leninskie Gori, 1/3, GSP-1, Moscow, Russia. Electronic address: aisina2004@mail.ru.
  • Mukhametova L; Chemical Enzymology Department, Chemistry Faculty, Lomonosov Moscow State University, 119991 Moscow, Leninskie Gori, 1/3, GSP-1, Moscow, Russia.
  • Ivanova E; Chemical Enzymology Department, Chemistry Faculty, Lomonosov Moscow State University, 119991 Moscow, Leninskie Gori, 1/3, GSP-1, Moscow, Russia.
Mater Sci Eng C Mater Biol Appl ; 109: 110605, 2020 Apr.
Article em En | MEDLINE | ID: mdl-32228918
BACKGROUND: Polyamidoamine (PAMAM) dendrimers are a new class of monodisperse polymers that are used for drug delivery in systemic administrations. The influence of PAMAM dendrimers on components of the blood coagulation system has been extensively studied, but their effect on the activity of the fibrinolysis system has not been studied to date. METHODS: The effect of cationic (G1-G3) and anionic (G1.5-G3.5) PAMAM dendrimers on the conformation and function of the main components of the coagulation and fibrinolysis systems was comparatively studied. Changes in overall plasma hemostatic potential, thrombin generation, prothrombin time, thrombin and tPA activities, the fluorescence of fibrinogen and plasminogen, zeta potential, polymerization of fibrinogen, and activation of plasminogen were analyzed to assess coagulofibrinolytic mechanisms of influence of the charge of the dendrimers. RESULTS: Cationic dendrimers increased prothrombin time, suppressed thrombin generation in plasma, and changed the conformation and coagulability of fibrinogen, while anionic dendrimers did not have such effects. Anionic dendrimers slightly reduced tPA activity and altered plasminogen conformation much more strongly than the cationic dendrimers. Plasminogen activation by tPA was strongly inhibited by anionic dendrimers and weakly stimulated by cationic dendrimers. All these effects were enhanced with increasing generation and concentration of the dendrimers. CONCLUSIONS: PAMAM-NH2 dendrimers inhibit the extrinsic activation pathway of the coagulation system and alter the conformation and function of fibrinogen. PAMAM-COOH dendrimers change the conformation of plasminogen and inhibit its activation by tPA. This study gives new insight into the effect of anionic PAMAM dendrimers on the activity of the fibrinolytic system. For intravenous applications, the antifibrinolytic effect of anionic PAMAM dendrimers of generation ≥G2.5 should be considered.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Coagulação Sanguínea / Hemostáticos Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Coagulação Sanguínea / Hemostáticos Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article