PAMAM complexes

The performance of several palladium piecatalysts, like palladium(n) acetate, palladium(0)NPs encapsulated into polyfamidoamine) (PAMAM) dendrimers (Pd DENs) and palladium(II)-PAMAM complexes, in the Stille reaction between trichloro(pheityl)stannane and iodoarenes in water was compared [26]. The reactivity of Pd DENs is sirttilar or inferior to that of palladium(II) acetate, although the presence of the derrdrimer suppresses the formation of homocouplirrg products and allows catalyst recycling. It is suggested that the reaction catalyzed by Pd DENs occtrrs via palladirrm species which are leached form the NP but which rerrrain co-ordirrated to the derrdritic macromolecule. 

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. 

Oral delivery is desirable due to the ease of administration, lower cost, and increased patient compliance. Despite these advantages, oral delivery of macromolecules is challenging due to low penetration across the intestinal epithelial barrier. To circumvent these barriers, drugs have been attached to mac-romolecular carriers such as dendrimers that can potentially aid in absorption across the intestinal epithelium. PAMAM dendrimers are effectively transported across epithelial barriers (Wiwattanapatapee et al. 2000 El-Sayed et al. 2002 Kitchens et al. 2006). SN-38, a potent anticancer drug, when complexed with PAMAM dendrimers showed increased solubility and uptake by Caco-2 cells (Kolhatkar et al. 2008). Orally administered anti-inflammatory drug ketoprofen in the form of PAMAM complexes (Man et al. 2006) prolonged activity and increased bio availability with a sustained release profile. 

Keywords. Polyamidoamine dendrimers. Activation of PAMAM dendrimers. Transfection, Gene transfer, DNA-dendrimer complex... 

PAMAM dendrimers have the following characteristics which are important for their use as transfection reagents. They bind and form complexes with nucleic acids, allow transfer of the DNA-dendrimer complex into the cytoplasm of the... 

Activated PAMAM dendrimers interact with DNA to form a DNA-dendrimer complex with a toroid-like structure (Fig. 2). Such DNA-dendrimer complexes have diameters of 50-100 nm [10],which means that the DNA molecules are highly condensed in these complexes. A 6-kb plasmid alone, for example, has an extended structure several hundred nanometers in diameter. In transfection experiments, typically an 8- to 12-fold excess of positive amino groups over negatively... 

Dendrimers bearing certain fluorescent molecules attached on their periphery have been shown to be environmentally sensitive probes for the presence of certain metal ions or to changes in pH (Balzani et al., 2000 Paola et al., 2005). In addition, PAMAM dendrimers modified with the relatively hydrophobic dye Oregon Green 488 were shown to be a more effective transfection agent for anti-sense oligonucleotides than the dendrimer alone-plus the complex could be tracked within the cell due to the fluorescence of the dye (Yoo and Juliano, 2000). 

Jacobsen et al. reported enhanced catalytic activity by cooperative effects in the asymmetric ring opening (ARO) of epoxides.[38] Chiral Co-salen complexes (Figure 4.27) were used, which were bound to different generations of commercial PAMAM dendrimers. As a direct consequence of the second-order kinetic dependence on the [Co(salen)] complex concentration of the hydrolytic kinetic resolution (HKR), reduction of the catalyst loading using monomeric catalyst leads to a sharp decrease in overall reaction rate. 

To investigate this dendritic effect, a dimeric model compound was synthesized which mimics the tethered relationship of two catalytic units within one branch of the PAMAM dendrimer. All dendritic catalysts were more active in the HKR than the parent complex. Furthermore, the dendritic catalysts also displayed significantly higher activity than the dimeric model compound. The authors proposed that this positive dendritic effect arises from restricted conformation imposed by the dendrimer structure, thereby creating a bigger effective molarity of [Co(salen)] units. Alternatively, the multimeric nature of the dendrimer, may lead to higher order in productive cooperative interactions between the catalytic units. 

The Lipari-Szabo approach was used to understand the cause of the pH-dependent relaxivities of PAMAM-type dendrimeric Gdm complexes (74). Three different generations (5,7,9) of PAMAM dendrimers loaded with the [Gd(EPTPA)(H20)]2 chelate via a benzyl-thiourea linkage have been investigated (Scheme 8). The relaxivities show a strong and reversible pH dependency for all three dendrimer complexes,... 

Scheme 8. Generation 5, 7, and 9 PAMAM dendrimers bearing [Gd(EPTPA)(H20)] complexes. The increase of relaxivity with decreasing pH is related to the protonation of the internal amines which, via electrostatic repulsion, leads to an increasing size of the dendrimer.

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... 

The surface morphologies of PAMAM dendrimers have been studied extensively by Turro and co-workers [16-23]. As shown in Scheme 4, one approach was to study the adsorption of organic dye molecules and metal complexes on the dendrimer surface by UY-Vis and fluorescence spectroscopy another approach took advantages of electron transfer processes between two adsorbed species on a single dendrimer surface or between the adsorbed species on a dendrimer surface and other species in aqueous solution. 

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