PAMAM dendrimers charge

In a study conducted by Liu et at, a doxorubicin (Dox)-carrier system was developed by electrostatic complexion of G4 PAMAM dendrimer with a pH-sensitive diblock copolymer of poly(methacryloyl sulfadimethoxine) (PSD) and PEG, with lactose (LA) coupled at the distal end of the PEG chain [77]. A higher cumulative Dox release from LA-PEG-b-PSD/PAMAM complexes was observed at pH 6.5 compared to pH 7. In another study, a pH-sensitive dendrimer nanoparticle was prepared, where surface cationic charge of the PAMAM dendrimer was reduced to prevent opsonization in the systemic circulation [78]. Zwitterionic chitosan (ZWC), a chitosan derivative with a unique pH-sensitive charge profile, was used to modify the cationic surface of PAMAM dendrimers. A stable electrostatic complex between ZWC and PAMAM was formed at pH 7.4, where the PAMAM dendrimer surface was covered with ZWC. The results demonstrated that ZWC can mask the surface charge, which minimizes hemolytic and cytotoxic activities of PAMAM dendrimers. However, the complex dissociated due to the charge conversion at low pH, allowing PAMAM dendrimer charge to be exposed and facilitate its entrance into the cells. 

PAMAM dendrimers provide a series of nearly precise macromolecules with almost equivalent charge density, yet a wide molecular weight range (a few hundred to almost a million), of which gel electrophoretic analysis can be carried out under native conditions [21],... 

In the first report, PAMAM dendrimers with primary amine surface groups were used [27]. It was found that complex formation is dependent both upon the size (generation) of the dendrimers used and the charge ratio between the (cationic and anionic species, i.e. ammonium groups on PAMAM to phosphate groups on DNA). Retardation of DNA migration was not observed with... 

PAMAM dendrimer G3 or lower generations at any charge ratio, while complete retardation with higher generations occurred only when an equivalent (charge ratio of 1) or excess dendrimer amine groups are present. 

The SANS experiments [51] were performed with solutions of G8 PAMAM dendrimer in D20, methyl-d4, ethyl-d6, and n-butyl-d10 alcohol at a temperature of T = 20.0 °C. PAMAM dendrimers do not dissolve in acetone, but they readily dissolve in methyl alcohol/acetone mixtures over a wide range of composition. Solvents of different composition, were prepared and added to a weighed amount of dried G5 or G8 dendrimer. In a separate set of experiments, the NIST NG7 30 m instrument was used to measure the effects of charging on the dendrimer size. PAMAM G8 dendrimers in D20 were charged by addition of HC1 in the presence of various amounts of NaCl to the charged dendrimers to screen the electrostatic interactions. 

A number of experimental in vivo gene therapy trials on animals using PAMAM dendrimers are in their preliminary stages. Numerous in vivo experiments are currently being conducted in order to optimize the dendrimer generation, concentration, and complex charge ratio to obtain optimal transfection efficiency. 

Chen W-R, Porcar L, Liu Y, Butler PD, Magid LI. Small angle neutron scattering studies of the counterion effects on the molecular conformation and strucmre of charged G4 PAMAM dendrimers in aqueous solutions. Macromolecules 2007 40 5887-5898. 

PAMAM dendrimers can condense DNA into small toroidal particles without altering the structure of the DNA (Bielinska et al., 1997). These complexes were shown to form via electrostatic interactions, by the observation that DNA binding affinity is directly proportional to the number of charged surface amines. When... 

This increase has two-fold implications. First, it implies that the fractured dendrimer is more flexible than the intact dendrimer and second, that the fractured dendrimer may expand due to an increase in positive charge at lower pH, a quantity that was described as essential for PEI mediated transfection. Indeed, when branched PEI was subjected to the same set of experiments, the same three-fold increase in viscosity was observed, lending support to the idea that PAMAM dendrimers act as proton sponges. Evidence of lysosomal buffering capability of PAMAM dendrimers was shown by Kukowska-Latallo et al. (1996) when they observed that the efficiency of G5-EDA dendrimers was enhanced by the addition of chloroquine, while the same molecule could not enhance transfection of G10-EDA dendrimers, which contain 40-fold more surface amine groups for proton absorption. 

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