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Analysis of biotinylated generation 4 poly(amidoamine) (PAMAM) dendrimer distribution in the rat brain and toxicity in a cellular model of the blood-brain barrier.

Authors
  • Hemmer, Ruth
  • Hall, Andrew
  • Spaulding, Robert
  • Rossow, Brett
  • Hester, Michael
  • Caroway, Megan
  • Haskamp, Anthony
  • Wall, Steven
  • Bullen, Heather A
  • Morris, Celeste
  • Haik, Kristi L
Type
Published Article
Journal
Molecules
Publisher
MDPI AG
Publication Date
Jan 01, 2013
Volume
18
Issue
9
Pages
11537–11552
Identifiers
DOI: 10.3390/molecules180911537
PMID: 24048286
Source
Medline
License
Unknown

Abstract

Dendrimers are highly customizable nanopolymers with qualities that make them ideal for drug delivery. The high binding affinity of biotin/avidin provides a useful approach to fluorescently label synthesized dendrimer-conjugates in cells and tissues. In addition, biotin may facilitate delivery of dendrimers through the blood-brain barrier (BBB) via carrier-mediated endocytosis. The purpose of this research was to: (1) measure toxicity using lactate dehydrogenase (LDH) assays of generation (G)4 biotinylated and non-biotinylated poly(amidoamine) (PAMAM) dendrimers in a co-culture model of the BBB, (2) determine distribution of dendrimers in the rat brain, kidney, and liver following systemic administration of dendrimers, and (3) conduct atomic force microscopy (AFM) on rat brain sections following systemic administration of dendrimers. LDH measurements showed that biotinylated dendrimers were toxic to cell co-culture after 48 h of treatment. Distribution studies showed evidence of biotinylated and non-biotinylated PAMAM dendrimers in brain. AFM studies showed evidence of dendrimers only in brain tissue of treated rats. These results indicate that biotinylation does not decrease toxicity associated with PAMAM dendrimers and that biotinylated PAMAM dendrimers distribute in the brain. Furthermore, this article provides evidence of nanoparticles in brain tissue following systemic administration of nanoparticles supported by both fluorescence microscopy and AFM.

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