A codendrimer of PAMAM decorated with oligoethylene glycol dendrons: Synthesis, self-assembly, and application as a drug carrier

A codendrimer of PAMAM covered with oligoethylene glycol (OEG) dendrons (PGD) was prepared, and its conjugation with the anti-cancer drug, vincristine (VCR), via the pH-sensitive imine bond (PGV), was investigated. Dynamic light scattering, transmission electron microscopy, and cryo-transmission electron microscopy demonstrated that PGD and PGV self-assembled into spherical aggregates with a mean diameter of approximately 120 nm, in aqueous solutions. The application of these two codendrimers as drug carriers was studied, with both PGD and PGV demonstrating a good capacity for the loading of VCR, exhibiting drug-loadings (DLs) as high as 43% (physical encapsulation) and 32% (reversible conjugation), respectively. The cytotoxicity of PGD and PGV were evaluated in vitro. Specifically, PGV behaved as a prodrug, releasing VCR at a nearly constant rate during a long period of 16 days, with no burst release in pH 5.5 PBS. Moreover, the in vitro drug release from PGV indicated a relatively faster VCR release in acidic environments. All of these properties revealed that PGV has good potential to be used for IV injectable anti-cancer drug release, especially in long-acting interventional chemotherapy.