Next Article in Journal
Next Article in Special Issue
Previous Article in Journal
Previous Article in Special Issue
Molecules 2013, 18(9), 11537-11552; doi:10.3390/molecules180911537
Article

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

1
, 1,2
, 1
, 1
, 1
, 1
, 2
, 2
, 2, 2,*  and 1,3,*
Received: 23 July 2013; in revised form: 3 September 2013 / Accepted: 10 September 2013 / Published: 17 September 2013
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
Download PDF [3257 KB, uploaded 18 June 2014]
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.
Keywords: dendrimers; atomic force microscopy; fluorescence microscopy; biotin; toxicity; blood brain barrier; lactate dehydrogenase assay dendrimers; atomic force microscopy; fluorescence microscopy; biotin; toxicity; blood brain barrier; lactate dehydrogenase assay
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Hemmer, R.; Hall, A.; Spaulding, R.; Rossow, B.; Hester, M.; Caroway, M.; Haskamp, A.; Wall, S.; Bullen, H.A.; Morris, C.; Haik, K.L. 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. Molecules 2013, 18, 11537-11552.

AMA Style

Hemmer R, Hall A, Spaulding R, Rossow B, Hester M, Caroway M, Haskamp A, Wall S, Bullen HA, Morris C, Haik KL. 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. Molecules. 2013; 18(9):11537-11552.

Chicago/Turabian Style

Hemmer, Ruth; Hall, Andrew; Spaulding, Robert; Rossow, Brett; Hester, Michael; Caroway, Megan; Haskamp, Anthony; Wall, Steven; Bullen, Heather A.; Morris, Celeste; Haik, Kristi L. 2013. "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." Molecules 18, no. 9: 11537-11552.



Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert