Structure/function relationships of polyamidoamine/DNA dendrimers as gene delivery vehicles

Chad S. Braun, Joseph A Vetro, Donald A. Tomalia, Gary S. Koe, Janet G. Koe, C. Russell Middaugh

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

PAMAM dendrimers are members of a class of polyamine polymers that demonstrate significant gene delivery ability. In this study, a selection of PAMAM dendrimers, spanning a range of sizes (generations 2, 4, 7, and 9) and transfection efficiencies, are characterized by various biophysical methods to search for structural properties that correlate with transfection. Measurements of colloidal properties (size and zeta potential) as a function of charge ratio reveal that highly transfecting dendrimer/DNA complexes have size/zeta potential values between 4 and 8. Circular dichroism (CD) and FTIR spectroscopy of complexes confirm the DNA component remains in B form when associated with all dendrimer generations up to a 5:1 charge ratio (±). Isothermal titration calorimetry and differential scanning calorimetry detect changes that are related to polymer structure and charge ratio but do not directly correlate with transfection efficiency. Despite DNA structural and stability changes detected by CD, FTIR, DSC, and ITC that are similar to those seen with other cationic delivery vehicles [e.g., cationic lipids, peptoids/lipitoids, peptides, polyethyleneimines (PEIs), etc.], clear correlations with transfection activity are not readily apparent. This may be due, at least in part, to the heterogeneity of the complexes.

Original languageEnglish (US)
Pages (from-to)423-436
Number of pages14
JournalJournal of Pharmaceutical Sciences
Volume94
Issue number2
DOIs
StatePublished - Jan 1 2005

Fingerprint

Dendrimers
Transfection
Genes
Zeta potential
DNA
Polymers
Peptoids
Fourier Transform Infrared Spectroscopy
Circular Dichroism
Polyethyleneimine
Polyamines
Calorimetry
Titration
Structural properties
Differential scanning calorimetry
Differential Scanning Calorimetry
Spectroscopy
Lipids
Spectrum Analysis
Peptides

Keywords

  • DNA
  • Dendrimers
  • Gene delivery
  • Structure/function analysis

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Structure/function relationships of polyamidoamine/DNA dendrimers as gene delivery vehicles. / Braun, Chad S.; Vetro, Joseph A; Tomalia, Donald A.; Koe, Gary S.; Koe, Janet G.; Middaugh, C. Russell.

In: Journal of Pharmaceutical Sciences, Vol. 94, No. 2, 01.01.2005, p. 423-436.

Research output: Contribution to journalArticle

Braun, Chad S. ; Vetro, Joseph A ; Tomalia, Donald A. ; Koe, Gary S. ; Koe, Janet G. ; Middaugh, C. Russell. / Structure/function relationships of polyamidoamine/DNA dendrimers as gene delivery vehicles. In: Journal of Pharmaceutical Sciences. 2005 ; Vol. 94, No. 2. pp. 423-436.
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