(358e) The Microstructure of Solvated Pegylated PAMAM Dendrimer Nanocarriers From Fully Atomistic Computer Simulations

Poly(amido-amine) (PAMAM) dendrimers are well-defined, highly branched, nanostructured polymers comprised of a core, branching units, and terminal functional groups.  Their unique structure, which is characterized by high monodispersity and the readily modifiable surface functional groups, make them very attractive in a variety of biomedical applications, including gene and drug delivery, and as imaging agents.  Polyethylene glycol (PEG) is one of the commonly used ligands to enhance PAMAM’s capability in drug delivery.  It helps to decrease cytotoxicity, increase retention times in systemic circulation, increase aqueous solubility, encapsulate and protect therapeutic molecules.  Understanding the microstructure of dendrimers nanocarriers (DNCs) and the PEG layers upon conjugation will help us optimize design for drug delivery applications.

In this work we present a microscopic view of the structure of solvated PEGylated PAMAM DNCs obtained through molecular dynamics simulations using atomistic models.  We report the results for from generation 2 (G₂) to G₅ PAMAM (G_xNH₂) dendrimers at different densities of PEGylation.  The results obtained showed a good match in size with experimental measurements reported.  No back-folding is observed for dendrimers with generation lower than G₄NH₂, and they do not assume a “globular” shape as it is usually depicted.  G₁-G₃ dendrimers show a dense-packed, non-globular structure, while G₄ and G₅ have a segmented, “open-type” structure.  PEGylation is observed to not only increase the overall size of the nanocarriers and decrease the solvation of primary amines, but it also serves to expand the core of the dendrimer and change their overall shape.  A detailed analysis will be provided.