Cytotoxicity and in vivo plasma kinetic behavior of surface-functionalized PAMAM dendrimers

Abstract

Understanding the molecular features responsible for the plasma kinetics of surface-modified polyamido amine (PAMAM) dendrimers is critical to explore novel biomedical applications for these nanomaterials. In this report, polyethylene glycol (PEG) and folic acid (FA) were employed to obtain partially-substituted PAMAM dendrimers as model biocompatible nanomaterials with different size, charge and surface functionality. Cytotoxicity assays on HEK cells at 1-500 μM concentration confirmed that PEG and FA incorporation increased the cell viability of PAMAM-based nanomaterials. Measurements of plasma kinetics in vivo revealed that PEG-PAMAM has an extended circulation time in mice blood (71.7 min) over native PAMAM (53.3 min) and FA-PAMAM (41.8 min). Molecular dynamics simulations revealed a direct relationship between circulation time and dendrimer size, thus providing valuable evidence to increase understanding about the modulation of functional properties of PAMAM-based systems through surface modification, and to guide future efforts on the rational design of novel biomedical nanomaterials.

Keywords: Drug nanocarriers; PAMAM dendrimers; Pharmacokinetics; Surface functionalization.