Studies towards biocompatibility of PAMAM dendrimers – Overall hemostasis potential and integrity of the human aortic endothelial barrier

Markowicz-Piasecka, Magdalena; Luczak, Emilia; Chałubiński, Maciej; Broncel, Marlena; Mikiciuk-Olasik, Elżbieta; Sikora, Joanna

doi:10.1016/j.ijpharm.2014.07.002

Cited by 31 publications

(26 citation statements)

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“…CPD possesses 48 or 96 (G3 and G4, respectively) (-NH(Et 2 ) 2 ) groups, PAMAM 32 and 64 (G3 and G4, respectively) -NH 2 groups, whereas CBD has 16 ammonium groups. Third, the molar mass and diameters are diverse (Caminade and Majoral, 2005;Markowicz-Piasecka et al, 2014). All these properties influence the interaction of dendrimers with both siRNAs and cells.…”

Section: Discussionmentioning

confidence: 99%

Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (B). Efficiency of pharmacological action

Dzmitruk

Szulc

Shcharbin

et al. 2015

International Journal of Pharmaceutics

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Section: Discussionmentioning

confidence: 99%

Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (B). Efficiency of pharmacological action

Dzmitruk

Szulc

Shcharbin

et al. 2015

International Journal of Pharmaceutics

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“…The CL-test, described previously by Kostka et al, (2007), was used to evaluate the effect of the metformin prodrugs on the overall potential of clot formation and fibrinolysis as well as its kinetic parameters. The test is based on the evaluation of the global assay of coagulation and fibrinolysis by measuring the changes in optical transmittance over time (Kostka et al, 2007;Markowicz-Piasecka et al, 2014). The CL-test is a modification of the optical measurement of coagulation and blood fibrinolysis previously described by Glover et al (Glover and Warner, 1975) and He et al(He et al, 1999;He et al, 2001).…”

Section: Clot Formation and Fibrinolysis Assay (Cl-test)mentioning

confidence: 99%

New prodrugs of metformin do not influence the overall haemostasis potential and integrity of the erythrocyte membrane

Markowicz-Piasecka

Sikora

Mateusiak

et al. 2017

European Journal of Pharmacology

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Although metformin, an oral anti-diabetic drug, has been found to have multidirectional effects over the past decade, it is characterised by unfavourable pharmacokinetic properties. This study discusses the effects of metformin, phenformin and three prodrugs of metformin on the haemostasis and integrity of Red Blood Cells (RBCs). The influence of examined biguanide derivatives on haemostasis was evaluated spectrophotometrically by clot formation and lysis test (CL-test) at 405nm. The extrinsic and intrinsic coagulation pathway were examined by measuring the PT (Prothrombin Time) and aPTT (Activated Partial Tromboplastin Time). Haemolysis assay, microscopy and flow cytometry studies were used to assess the effect of the tested compounds on RBCs. Although none of the tested biguanide derivatives significantly influenced the overall potential of clot formation and fibrinolysis (CL constants), statistically significant changes were seen in the values of the kinetic parameters of fibrinolysis. Furthermore, only prodrug 2, with an 8-carbon alkyl chain, unfavourably affected RBCs by interaction with the erythrocyte membrane leading to significant haemolysis. Our results provide a further insight into the effects of metformin and its prodrugs on haemostasis and RBCs and underscore the necessity for further research.

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“…Studies of PAMAM distribution on biological samples are rather scarce [79][80][81][82]. For example, Dobrovolskaia et al [79] reported in in vitro studies the effects of the size and surface terminal groups of PAMAM dendrimers on healthy human platelets.…”

Section: Discussionmentioning

confidence: 99%

Selective aggregation of PAMAM dendrimer nanocarriers and PAMAM/ZnPc nanodrugs on human atheromatous carotid tissues: a photodynamic therapy for atherosclerosis

Spyropoulos-Antonakakis¹,

Sarantopoulou²,

Trohopoulos³

et al. 2016

Nano Online

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Photodynamic therapy (PDT) involves the action of photons on photosensitive molecules, where atomic oxygen or OH − molecular species are locally released on pathogenic human cells, which are mainly carcinogenic, thus causing cell necrosis. The efficacy of PDT depends on the local nanothermodynamic conditions near the cell/nanodrug system that control both the level of intracellular translocation of nanoparticles in the pathogenic cell and their agglomeration on the cell membrane. Dendrimers are considered one of the most effective and promising drug carriers because of their relatively low toxicity and negligible activation of complementary reactions. Polyamidoamine (PAMAM) dendrite delivery of PDT agents has been investigated in the last few years for tumour selectivity, retention, pharmacokinetics and water solubility. Nevertheless, their use as drug carriers of photosensitizing molecules in PDT for cardiovascular disease, targeting the selective necrosis of macrophage cells responsible for atheromatous plaque growth, has never been investigated. Furthermore, the level of aggregation, translocation and nanodrug delivery efficacy of PAMAM dendrimers or PAMAM/zinc phthalocyanine (ZnPc) conjugates on human atheromatous tissue and endothelial cells is still unknown. In this work, the aggregation of PAMAM zero generation dendrimers (G0) acting as drug delivery carriers, as well as conjugated G0 PAMAM dendrimers with a ZnPc photosensitizer, to symptomatic and asymptomatic human carotid tissues was investigated by using atomic force microscopy (AFM). For the evaluation of the texture characteristics of the AFM images, statistical surface morphological and fractal analytical methodologies and Minkowski functionals were used. All statistical quantities showed that the deposition of nanodrug carriers on healthy tissue has an inverse impact when comparing to the deposition on atheromatous tissue with different aggregation features between G0 and G0/ZnPc nanoparticles and with considerably larger G0/ZnPc aggregations on the atheromatous plaque. The results highlight the importance of using PAMAM dendrimer carriers as a novel and promising PDT platform for atherosclerosis therapies.

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Studies towards biocompatibility of PAMAM dendrimers – Overall hemostasis potential and integrity of the human aortic endothelial barrier

Cited by 31 publications

References 50 publications

Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (B). Efficiency of pharmacological action

Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (B). Efficiency of pharmacological action

New prodrugs of metformin do not influence the overall haemostasis potential and integrity of the erythrocyte membrane

Selective aggregation of PAMAM dendrimer nanocarriers and PAMAM/ZnPc nanodrugs on human atheromatous carotid tissues: a photodynamic therapy for atherosclerosis

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