Interactions between maltose functionalized hyperbranched poly(ethylene imine)s (95% maltose decoration denoted as Mal-PEI A; 33% maltose decoration denoted as Mal-PEI B) and red blood cells (RBCs) and between red blood cell membranes were investigated. We monitored the degree of hemolysis, the change in cell shape, the influence of polymers on the fluidity of the cell membrane and some cell membrane enzymes to determine their possible cytotoxic impact on them. To observe the extent of hemolysis, the RBCs were incubated with different concentrations of Mal-PEIs. The first significant lysis of RBCs was observed after 6h of incubation. Prolongation of the incubation time increased the number of ruptured cells. Moreover, we observed that Mal-PEI B was more hemolytic than Mal-PEI A in buffer solution. In contrast, an incubation of RBCs with Mal-PEIs in human plasma significantly decreased the hemolytic process and showed higher hemolytic property of Mal-PEI A compared to Mal-PEI B. Also several changes in the shape of the RBCs occurred after incubation with Mal-PEIs. Some of the erythrocytes shrank (echinocytes), but their morphology generally remained unchanged during the incubation. As shown by fluorescence experiments, both polymers induced the increase of fluidity of RBCs membranes. In summary, both types of hyperbranched poly(ethylene imine)s were practically non-hemolytic even at high polymer concentrations. Mal-PEI B was slightly more noxious than the Mal-PEI A in a buffer solution, while in blood plasma, the situation was opposite. Decrease of Na+/K+ ATPase and total ATPase enzymes activity was related with molecule size and number of maltose groups on the surface of molecule. The low hemolytic properties only observed at higher concentration (100μM and 400μM) indicated that Mal-PEIs are promising macromolecules in the area of drug delivery systems.

• Klíčová slova
• Dendritic glycopolymer, Erythrocytes, Hemolysis, Nanoparticles,
• MeSH
• adenosintrifosfatasy metabolismus   MeSH
• erytrocytární membrána účinky léků   MeSH
• erytrocyty účinky léků   MeSH
• fluorescenční spektrometrie MeSH
• iminy chemie   farmakologie   MeSH
• lidé MeSH
• maltosa chemie   farmakologie   MeSH
• nanočástice MeSH
• polyethyleny chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosintrifosfatasy MeSH
• iminy MeSH
• maltosa MeSH
• poly(ethylene imine) MeSH Prohlížeč
• polyethyleny MeSH

The influence of maltose-modified poly(propylene imine) (PPI) dendrimers on dimyristoylphosphatidylcholine (DMPC) or dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) (3%) liposomes was studied. Fourth generation (G4) PPI dendrimers with primary amino surface groups were partially (open shell glycodendrimers - OS) or completely (dense shell glycodendrimers - DS) modified with maltose residues. As a model membrane, two types of 100nm diameter liposomes were used to observe differences in the interactions between neutral DMPC and negatively charged DMPC/DMPG bilayers. Interactions were studied using fluorescence spectroscopy to evaluate the membrane fluidity of both the hydrophobic and hydrophilic parts of the lipid bilayer and using differential scanning calorimetry to investigate thermodynamic parameter changes. Pulsed-filed gradient NMR experiments were carried out to evaluate common diffusion coefficient of DMPG and DS PPI in D2O when using below critical micelle concentration of DMPG. Both OS and DS PPI G4 dendrimers show interactions with liposomes. Neutral DS dendrimers exhibit stronger changes in membrane fluidity compared to OS dendrimers. The bilayer structure seems more rigid in the case of anionic DMPC/DMPG liposomes in comparison to pure and neutral DMPC liposomes. Generally, interactions of dendrimers with anionic DMPC/DMPG and neutral DMPC liposomes were at the same level. Higher concentrations of positively charged OS dendrimers induced the aggregation process with negatively charged liposomes. For all types of experiments, the presence of NaCl decreased the strength of the interactions between glycodendrimers and liposomes. Based on NMR diffusion experiments we suggest that apart from electrostatic interactions for OS PPI hydrogen bonds play a major role in maltose-modified PPI dendrimer interactions with anionic and neutral model membranes where a contact surface is needed for undergoing multiple H-bond interactions between maltose shell of glycodendrimers and surface membrane of liposome.

• Klíčová slova
• Glycodendrimer, Hydrogen bond, Ionic force, Liposomes, Model membranes,
• MeSH
• dendrimery chemie   metabolismus   MeSH
• difenylhexatrien chemie   MeSH
• diferenciální skenovací kalorimetrie MeSH
• dimyristoylfosfatidylcholin chemie   metabolismus   MeSH
• fluidita membrány MeSH
• fluorescenční polarizace MeSH
• fosfatidylglyceroly chemie   metabolismus   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lipidové dvojvrstvy chemie   metabolismus   MeSH
• liposomy chemie   metabolismus   MeSH
• magnetická rezonanční spektroskopie MeSH
• maltosa chemie   metabolismus   MeSH
• membránové lipidy chemie   metabolismus   MeSH
• polypropyleny chemie   metabolismus   MeSH
• statická elektřina MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dendrimery MeSH
• difenylhexatrien MeSH
• dimyristoylfosfatidylcholin MeSH
• dimyristoylphosphatidylglycerol MeSH Prohlížeč
• fosfatidylglyceroly MeSH
• lipidové dvojvrstvy MeSH
• liposomy MeSH
• maltosa MeSH
• membránové lipidy MeSH
• poly(propyleneimine) MeSH Prohlížeč
• polypropyleny MeSH