Nanoparticle diffusion in, and microrheology of, the bovine vitreous ex vivo

Qingguo Xu, Nicholas J. Boylan, Jung Soo Suk, Ying Ying Wang, Elizabeth A. Nance, Jeh Chang Yang, Peter J McDonnell, Richard A. Cone, Elia J Duh, Justin S Hanes

Research output: Contribution to journalArticle

Abstract

Intravitreal injection of biodegradable nanoparticles (NP) holds promise for gene therapy and drug delivery to the back of the eye. In some cases, including gene therapy, NP need to diffuse rapidly from the site of injection in order to reach targeted cell types in the back of the eye, whereas in other cases it may be preferred for the particles to remain at the injection site and slowly release drugs that may then diffuse to the site of action. We studied the movements of polystyrene (PS) NP of various sizes and surface chemistries in fresh bovine vitreous. PS NP as large as 510 nm rapidly penetrated the vitreous gel when coated with polyethylene glycol (PEG), whereas the movements of NP 1190 nm in diameter or larger were highly restricted regardless of surface chemistry owing to steric obstruction. PS NP coated with primary amine groups (NH 2) possessed positively charged surfaces at the pH of bovine vitreous (pH = 7.2), and were immobilized within the vitreous gel. In comparison, PS NP coated with COOH (possessing negatively charged surfaces) in the size range of 100-200 nm and at particle concentrations below 0.0025% (w/v) readily diffused through the vitreous meshwork; at higher concentrations (~ 0.1% w/v), these nanoparticles aggregated within vitreous. Based on the mobility of different sized PEGylated PS NP (PS-PEG), we estimated the average mesh size of fresh bovine vitreous to be ~ 550 ± 50 nm. The bovine vitreous behaved as an impermeable elastic barrier to objects sized 1190 nm and larger, but as a highly permeable viscoelastic liquid to non-adhesive objects smaller than 510 nm in diameter. Guided by these studies, we next sought to examine the transport of drug- and DNA-loaded nanoparticles in bovine vitreous. Biodegradable NP with a diameter of 227 nm, composed of a poly(lactic-co-glycolic acid) (PLGA)-based core coated with poly(vinyl alcohol) rapidly penetrated vitreous. Rod-shaped, highly-compacted CK30PEG10k/DNA with PEG coating (neutral surface charge; hydrodynamic diameter ~ 60 nm) also diffused rapidly within vitreous. These findings will help guide the development of nanoparticle-based therapeutics for the treatment of vision-threatening ocular diseases.

Original languageEnglish (US)
Pages (from-to)76-84
Number of pages9
JournalJournal of Controlled Release
Volume167
Issue number1
DOIs
StatePublished - Apr 10 2013

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Nanoparticles
Polystyrenes
Genetic Therapy
Gels
Intravitreal Injections
Injections
Eye Diseases
DNA
Hydrodynamics
Pharmaceutical Preparations
Amines
Alcohols

Keywords

  • Drug delivery
  • Eye
  • Gene delivery
  • Nanotechnology
  • Particle tracking

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Nanoparticle diffusion in, and microrheology of, the bovine vitreous ex vivo. / Xu, Qingguo; Boylan, Nicholas J.; Suk, Jung Soo; Wang, Ying Ying; Nance, Elizabeth A.; Yang, Jeh Chang; McDonnell, Peter J; Cone, Richard A.; Duh, Elia J; Hanes, Justin S.

In: Journal of Controlled Release, Vol. 167, No. 1, 10.04.2013, p. 76-84.

Research output: Contribution to journalArticle

Xu, Qingguo ; Boylan, Nicholas J. ; Suk, Jung Soo ; Wang, Ying Ying ; Nance, Elizabeth A. ; Yang, Jeh Chang ; McDonnell, Peter J ; Cone, Richard A. ; Duh, Elia J ; Hanes, Justin S. / Nanoparticle diffusion in, and microrheology of, the bovine vitreous ex vivo. In: Journal of Controlled Release. 2013 ; Vol. 167, No. 1. pp. 76-84.
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