The influence of PAMAM-OH dendrimers on the activity of human erythrocytes ATPases

Abstract

Dendrimers are a relatively new and still not fully examined group of polybranched polymers. In this study polyamidoamine dendrimers with hydroxyl surface groups (PAMAM-OH) of third, fourth and fifth generation (G3, G4 and G5) were examined for their ability to influence the activity of human erythrocyte plasma membrane adenosinetriphosphatases (ATPases). Plasma membrane ATPases are a group of enzymes related, among others, to the maintenance of ionic balance inside the cell. An inhibition of their activity may result in a disturbance of cell functioning. Two of examined dendrimers (G4 and G5) were found to inhibit the activity of Na(+)/K(+) ATPase and Ca(2+) ATPase by 20-30%. The observed effect was diminished when higher concentrations of dendrimers were used. The experiment with the use of pyrene as fluorescent probe sensitive to the changes in microenvironment's polarity revealed that it was an effect of dendrimers' self-aggregation. Additional studies showed that PAMAM-OH dendrimers were able to decrease the fluidity of human erythrocytes plasma membrane. Obtained results suggest that change in plasma membrane fluidity was not caused by the dendrimer-lipid interaction, but dendrimer-protein interaction. Different pattern of influence of dendrimers on ATPases activity and erythrocyte membrane fluidity suggests that observed change in ATPases activity is not a result of dendrimer-lipid interaction, but may be related to direct interaction between dendrimers and ATPases.

Effects of PAMAM dendrimers with various surface functional groups and multiple generations on cytotoxicity and neuronal differentiation using human neural progenitor cells

“…PAMAM-NH 2 , one of the cationic dendrimers, is a positively charged particle, because of the protonation equilibria (Cakara et al, 2003;Cakara and Borkovec, 2007). In contrast, PAMAM-OH dendrimers did not affect the activity of human erythrocyte ATPase (Ciolkowski et al, 2011b), but positively surface-charged polystyrene particles induced platelet aggregation (Mayer et al, 2009;Dobrovolskaia et al, 2012). These reports suggest that dendrimer-induced cytotoxicity may cause by the surface charge of the dendrimers.…”

“…The effect of surface modifications to PAMAM dendrimers on their cytotoxicity has been studied previously (Hernando et al, 2012;Ciolkowski et al, 2011b), and amine-terminated (NH 2 ) PAMAM dendrimers were associated with a higher cytotoxic response. The effect of PAMAM dendrimer generation on their cytotoxicity was also investigated using an in vitro experiment that examined high-generation (G4, G5, and G6) PAMAM dendrimers (Mukherjee et al, 2010a(Mukherjee et al, , 2010bMaher et al, 2014).…”

Interaction of curcumin nanoformulations with human plasma proteins and erythrocytes

“…70 This activity may also depend on the type of dendrimer generated. 71 Nanoparticle interactions with erythrocytes cause abnormal membrane proteins and lipids that lead to the destruction of erythrocyte integrity and hemolysis. To investigate why some curcumin formulations are toxic to erythrocytes at 100 µM, binding of nanoparticles and red blood cells was investigated using transmission electron microscopy.…”

“…71 Altogether, these results provide an interesting insight into the correlation between various curcumin nanoformulations and protein interactions that may impact in vivo efficacy. From the analysis of protein binding and hemolysis experiments, it can be concluded that all the curcumin nanoformulations behave differently than the dendrimer curcumin formulation.…”

Novel Citric Acid Dendritic Hydrogels for the Delivery of Econazole Nitrate and its Antifungal Activity

“…Technique adapted for performing Zeta Potential was Dynamic Light Scattering Technique. The values of Zeta potential for Econazole loaded dendrimers ranged from -37 to -48, indicating good stability of the formulations (Ciolkowski et al, 2011). Stability of the formulations is contributed to the smaller dendritic size and repulsive electrostatic forces of dendrimers (Table no.4).…”