Acetyl-terminated PAMAM dendrimers for pH-sensitive delivery of irinotecan and fluorouracil: A molecular dynamics simulation study

[Display omitted] •G4ACE forms a stable complex with 6 IRI and 5 FLU molecules at neutral pH.•The loading capacity of G4ACE is 5 IRI and 2 FLU molecules at low pH.•Drug molecules prefer to interact with G4ACE via conjugation on the surface.•The ΔGbind at neutral pH is −17.4 and −5.9 kcal.mol−1 for IRI and FLU, respectively.•The ΔGbind at acidic pH is −11.8 and −2.1 kcal.mol−1, for IRI and FLU, respectively. Acetyl-terminated poly(amidoamine) dendrimer (G4ACE) was investigated as a pH-responsive nanocarrier for co-delivery of irinotecan (IRI) and fluorouracil (FU) using molecular dynamics simulations. The loading capacity of G4ACE at low pH is lower than that of physiological conditions. Drug molecules prefer to interact with dendrimer through conjugation on the surface monomers. The calculated ΔGbind for G4ACE:xIRI:yFU at neutral pH is about −17.4 and −5.9 kcal.mol−1 for IRI and FU, respectively; while, the corresponding values at acidic environment are −11.8 and −2.1 kcal.mol−1, respectively. Thus, when the complex reaches the acidic environment of cancer cells, it quickly releases the bound FU molecules.