Aqueous poly(amidoamine) dendrimer G3 and G4 generations with several interior cores at pHs 5 and 7: a molecular dynamics simulation study.

Poly(amidoamine) (PAMAM) dendrimers play an important role in drug delivery systems, because the dendrimers are susceptible to gain unique features with modification of their structure such as changing their terminals or improving their interior core. To investigate the core improvement and the effect of core nature on PAMAM dendrimers, we studied two generations G3 and G4 PAMAM dendrimers with the interior cores of commonly used ethylendiamine (EDA), 1,5-diaminohexane (DAH), and bis(3-aminopropyl) ether (BAPE) solvated in water, as an aqueous dendrimer system, by using molecular dynamics simulation and applying a coarse-grained (CG) dendrimer force field. To consider the electrostatic interactions, the simulations were performed at two protonation states, pHs 5 and 7. The results indicated that the core improvement of PAMAM dendrimers with DAH produces the largest size for G3 and G4 dendrimers at both pHs 5 and 7. The increase in the size was also observed for BAPE core but it was not so significant as that for DAH core. By considering the internal structure of dendrimers, it was found that PAMAM dendrimer shell with DAH core had more cavities than with BAPE core at both pHs 5 and 7. Also the moment of inertia calculations showed that the generation G3 is more open-shaped and has higher structural asymmetry than the generation G4. Possessing these properties by G3, specially due to its structural asymmetry, make penetration of water beads into the dendrimer feasible. But for higher generation G4 with its relatively structural symmetry, the encapsulation efficiency for water molecules can be enhanced by changing its core to DAH or BAPE. It is also observed that for the higher generation G4 the effect of core modification is more profound than G3 because the core modification promotes the structural asymmetry development of G4 more significantly. Comparing the number of water beads that penetrate into the PAMAM dendrimers for EDA, DAH, and BAPE cores indicates a significant increase when their cores have been modified with DAH or BAPE and substantiates the effective influence of the core nature in the dendrimer encapsulation efficiency.