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

Carola Diaz, Carolina Benitez, Felipe Vidal, Luis F. Barraza, Verónica A. Jiménez, Leonardo Guzman, Jorge Fuentealba, Gonzalo E. Yevenes, Joel B. Alderete

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2227-2234
Number of pages8
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number7
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • Drug nanocarriers
  • PAMAM dendrimers
  • Pharmacokinetics
  • Surface functionalization

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • General Materials Science
  • Pharmaceutical Science

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