May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Quaternary Ammonium β-Cyclodextrin Nanoparticles for Drug Delivery Across the Blood Retina/Brain Barriers
Author Affiliations & Notes
  • T. Lowe
    Surgery, Bioengineering , Materials Sci & Eng, Pennsylvania State University, Hershey, Pennsylvania
  • E. S. Gil
    Surgery, Bioengineering , Materials Sci & Eng, Pennsylvania State University, Hershey, Pennsylvania
  • J. S. Li
    Chemical Engineering, University of New Brunswick, Fredericton, New Brunswick, Canada
  • H. N. Xiao
    Chemical Engineering, University of New Brunswick, Fredericton, New Brunswick, Canada
  • Footnotes
    Commercial Relationships  T. Lowe, None; E.S. Gil, None; J.S. Li, None; H.N. Xiao, None.
  • Footnotes
    Support  Wallace H. Coulter Foundation
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4796. doi:https://doi.org/
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      T. Lowe, E. S. Gil, J. S. Li, H. N. Xiao; Quaternary Ammonium β-Cyclodextrin Nanoparticles for Drug Delivery Across the Blood Retina/Brain Barriers. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4796. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : The primary objective of this study is to evaluate cationic β-cyclodextrin nanoparticles containing quaternary ammonium groups (QAβCD nanoparticles) as drug delivery carriers for doxorubicin (Doxo) across the blood retinal barrier (BRB) or blood brain barrier (BBB) using an in vitro BRB or BBB model.

Methods: : The particle sizes and zeta potentials of novel QAβCD nanoparticles were characterized by a dynamic light scattering instrument and a Zeta potentiometer, respectively. We evaluated the effect of charge density of QAβCD nanoparticles on the endothelial toxicity, the tight junction integrity and permeability of QAβCD nanoparticles with/without Doxo across bovine brain microvessel endothelial cell (BBMVEC) monolayer, an in vitro BBB model; and bovine retinal endothelial cell (BREC) monolayer, an in vitro BRB model. We also tested the cell death effect of QAβCD nanoparticle/Doxo complexes on U87 tumor cells.

Results: : The hydrodynamic sizes of QAβCD nanoparticles were around 100 ~ 130 nm and their charge density was tunable. QAβCD nanoparticles did not change the integrity of BBMVEC monolayers. The permeability increased with the increase of quaternary ammonium groups. QAβCD nanoparticles not only were twice as permeable as 4 kD dextran control, but also enhanced Doxo permeability by a factor of 2.2 across the BBMVEC monolayer. Furthermore, QAβCD nanoparticle/Doxo complexes showed less cytotoxicity to BBMVECs than free Doxo after 4 h exposure, whereas QAβCD nanoparticle/Doxo complexes killed U87 tumor cells as effectively as free Doxo after 60 hr exposure.

Keywords: retina 
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