Generation 2 (G2) – Generation 4 (G4) PAMAM dendrimers disrupt key plasma coagulation parameters

Markowicz-Piasecka, Magdalena; Sadkowska, Adrianna; Podsiedlik, Maria; Mikiciuk-Olasik, Elżbieta; Sikora, Joanna

doi:10.1016/j.tiv.2019.04.010

Cited by 7 publications

(6 citation statements)

References 56 publications

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“…Initially developed as drug carriers, dendritic polymers such as polyamide amine (PAMAM) exhibit a broad spectrum of biological activity, as indicated by recent research . In particular, positively charged dendritic macromolecules can engage in electrostatic interactions with fibrinogen, leading to a significant decrease in factor X activity and the APTT and PT extended to 108.7 and 25.1 s, respectively, significantly higher than the blank control (35.8 and 11.7 s) . Similarly, dendritic poly(glycerol sulfate) (dPGS) based on dendritic polyglycerol (dPG) was originally investigated as a drug with anticoagulant activity.…”

Section: Synthetic Anticoagulant Macromolecules: Aliphatic Aromatic A...mentioning

confidence: 99%

Anticoagulant Macromolecules

et al. 2023

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Anticoagulant macromolecules have gained widespread use in the clinical treatment of cardiovascular diseases, blood-contacting or implantable materials, and medical devices due to their excellent anticoagulant properties. Inspired by the molecular characteristics of physiological anticoagulants that play a vital role in normal human coagulation and anticoagulation mechanisms, diverse anticoagulant macromolecules with special molecular structures and functional groups have been developed, where they can be systematically applied to the biomedical field. In this Perspective, the history and the recent progress of synthetic methods for anticoagulant macromolecules obtained by purification of natural products, semisynthetic methods, and synthetic methods are discussed from the aspect of molecular design. The critical application and immense development potential of these anticoagulant macromolecules in the field of clinical treatment and biomedicine is proposed.

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Section: Synthetic Anticoagulant Macromolecules: Aliphatic Aromatic A...mentioning

confidence: 99%

Anticoagulant Macromolecules

et al. 2023

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“…15 Markowicz et al also deemed that unlike G4 PAMAM, G2 and G3 PAMAM do not show procoagulant properties. 34 In this study, PAMAM dendrimers with a positive outer layer were employed to modify Ti, and these decorated substrates possessed favorable anticlotting properties. According to existing reports, primary amines in dendrimers can be protonated in a physiological fluid medium (pH 7.4).…”

Section: Molecularmentioning

confidence: 99%

“…36 In a previous study, selected cationic G3 PAMAM dendrimers showed a low toxic effect on ECs and were established to not trigger the expression of membrane-bound TF, suggesting that an extrinsic coagulation pathway was inactive. 34 Thus, in this study, only soluble TF was tested after ECs interacted with the materials. The results indicate that the fixed dendrimers also do not increase the soluble TF expression, meeting the requirements of modification in blood contact materials.…”

Section: Molecularmentioning

confidence: 99%

“…Dobrovolskaia et al showed that large-sized cationic dendrimers (G4–G6 PAMAM), and not small (G3) cationic/anionic/neutral ones, enable platelet congregation by obstructing membrane integrality, instead of conventional pathways . Markowicz et al also deemed that unlike G4 PAMAM, G2 and G3 PAMAM do not show procoagulant properties . In this study, PAMAM dendrimers with a positive outer layer were employed to modify Ti, and these decorated substrates possessed favorable anticlotting properties.…”

Section: Discissionmentioning

confidence: 99%

“…Numerous stimuli have been shown to stimulate TF production form ECs, including TNF-α, lipopolysaccharide, IL-1β, thrombin, or oxidized low-density lipoproteins . In a previous study, selected cationic G3 PAMAM dendrimers showed a low toxic effect on ECs and were established to not trigger the expression of membrane-bound TF, suggesting that an extrinsic coagulation pathway was inactive . Thus, in this study, only soluble TF was tested after ECs interacted with the materials.…”

Section: Discissionmentioning

confidence: 99%

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Proactive Hemocompatibility Platform Initiated by PAMAM Dendrimer Adapting to Key Components in Coagulation System

Wei

Wang

et al. 2022

Mol. Pharmaceutics

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Surface modification manipulates the application performance of materials, and thrombosis caused by material contact is a key risk factor of biomaterials failure in bloodcontacting/implanting devices. Therefore, building a safe and effective hemocompatibility platform is still urgent. Owing to the unique properties of polyamidoamine (PAMAM) dendrimers, in this study, modified surfaces with varying dendrimer densities were interacted with elements maintaining blood homeostasis. These included the plasma proteins bovine serum albumin and fibrinogen, cells in blood (platelets and erythrocyte), as well as endothelial cells (ECs), and the objective was to evaluate the blood compatibility of the chosen materials. Whole blood test and dynamic blood circulation experiment by the arteriovenous shunt mode of rabbit were also conducted, based on the complexity and fluidity of blood. The PAMAM-modified substrates, particularly that with a high density of PAMAM (N1.0), adsorbed proteins with lessened fibrinogen adsorption, reduced platelet activation and aggregation, and suppressed clotting in whole blood and dynamic blood testing. Furthermore, the designed PAMAM dendrimer densities were safe and showed negligible erythrocyte lysis. Concurrently, PAMAM modification could maintain EC growth and did not trigger the release of procoagulant factors. These results suggest that the PAMAM-modified materials are compatible for maintaining blood homeostasis. Thus, PAMAM dendrimers can work as excellent surface modifiers for constructing a hemocompatibility platform and even a primer layer for desired functional design, promoting the service performance of blood-contacting devices.

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Dendrimers in the context of targeting central nervous system disorders

Palan

Chatterjee

2022

Journal of Drug Delivery Science and Technology

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Generation 2 (G2) – Generation 4 (G4) PAMAM dendrimers disrupt key plasma coagulation parameters

Cited by 7 publications

References 56 publications

Anticoagulant Macromolecules

Anticoagulant Macromolecules

Proactive Hemocompatibility Platform Initiated by PAMAM Dendrimer Adapting to Key Components in Coagulation System

Dendrimers in the context of targeting central nervous system disorders

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