Thermochemical and spectroscopic studies on the supramolecular complex of PAMAM-NH2 G4 dendrimer and 5-fluorouracil in aqueous solution

Effect of PEGylation on the Structure and Drug Loading Capacity of PAMAM-G4 Dendrimers: A Molecular Modeling Approach on the Complexation of 5-Fluorouracil with Native and PEGylated PAMAM-G4

“…Estimated average stoichiometries for 5‐FU:PAMAM‐G4 and 5‐FU:PEG‐PAMAM‐G4 complexes are reported in Table together with the estimated number internally and externally complexed 5‐FU molecules. The average stoichiometries obtained for 5‐FU:PAMAM‐G4 complex (22:1) are in very good agreement with the experimental report by Buczkowski et al from the analysis of isothermal titration calorimetry (ITC) data, in which a number of 25 ± 3 binding centers per PAMAM‐G4 molecule have been determined . This constitutes a highly auspicious result considering the extent of the simulated systems and the sampling limitations of classical MD simulation.…”

“…The main goals of our work are to examine the effect of PEGylation on the structure and drug loading capacity of PAMAM‐G4 dendrimer, and to evaluate the validity of our computational approach to predict experimental properties that are relevant for the rational design and optimization of PAMAM‐based drug delivery systems, such as the complex stoichiometry and differential distribution of the drug within internal PAMAM branches and external PEG chains. MD simulations were performed by mimicking neutral pH conditions (pH = 7.4), for which experimental information concerning the complexation of 5‐FU with PAMAM‐G4 is available . In addition, it has been reported that the drug–dendrimer association with PAMAM dendrimers is enhanced at neutral pH respect to acidic and basic pH environments .…”

Spectroscopic and calorimetric studies of formation of the supramolecular complexes of PAMAM G5-NH2 and G5-OH dendrimers with 5-fluorouracil in aqueous solution

“…S1) as well as the mixtures of this drug and PAMAM G5-OH (Fig. S2) in heavy water as in previous 1 H NMR studies of PAMAM-NH 2 (Bányai et al, 2013;Barra et al, 2014a,b;Buczkowski et al, 2012bBuczkowski et al, , 2013Cao et al, 2013;Giri et al, 2011;Hu et al, 2010Hu et al, , 2012Keri et al, 2015) and PAMAM-OH dendrimers (Choi et al, 2012;Giri et al, 2011;Gomez et al, 2009a,b;Hu et al, 2012;Pellechia et al, 2004;Wang et al, 2013). With increasing the concentration of 5-fluorouracil in the mixture of drug and dendrimer one can observe that peak at 2.6 ppm corresponding to the protons of methylene groups present at tertiary amine groups is not clearly shifted during the drug bonding by cationic PAMAM G5-NH 2 dendrimer (Fig.…”

“…Analyzing changes in the chemical shifts of the proton groups of dendrimer macromolecule under the influence of increasing ligand concentration, one can calculate the bonding parameters by the method of non-linear multi-parameter regression, using the following equation (Buczkowski et al, 2012b(Buczkowski et al, , 2013Fielding, 2007;Hu et al, 2010Hu et al, , 2012:…”

Effect of the Structure of Therapeutic Adenosine Analogues on Stability and Surface Electrostatic Potential of their Complexes with Poly(propyleneimine) Dendrimers

“…Thus, the detection of potential active sites with lower affinity and/or located deeper within the structure is hindered due to the limited diffusion of the drug to the interior of the PPI macromolecules. As a result, the tested system does not fully reach thermodynamic equilibrium, and the number of determined binding sites may be lower compared to the results obtained with more static techniques (such as dialysis or ultrafiltration) that allow for the detection of active sites with lower affinity . Moreover, assuming the predominance of surface interactions over encapsulation inside the dendritic scaffold, the model of a single type of bonding centers to describe the thermodynamic parameters of complexation processes is commonly applied in ITC measurements .…”