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Review
. 2015;6(12):1365-76.
doi: 10.4155/tde.15.75.

Nanostructured materials for ocular delivery: nanodesign for enhanced bioadhesion, transepithelial permeability and sustained delivery

Jean Kim  1 , Erica B Schlesinger  1 , Tejal A Desai  2
Affiliations
Review

Nanostructured materials for ocular delivery: nanodesign for enhanced bioadhesion, transepithelial permeability and sustained delivery

Jean Kim et al. Ther Deliv. 2015.

Abstract

Effective drug delivery to the eye is an ongoing challenge due to poor patient compliance coupled with numerous physiological barriers. Eye drops for the front of the eye and ocular injections for the back of the eye are the most prevalent delivery methods, both of which require relatively frequent administration and are burdensome to the patient. Novel drug delivery techniques stand to drastically improve safety, efficacy and patient compliance for ocular therapeutics. Remarkable advances in nanofabrication technologies make the application of nanostructured materials to ocular drug delivery possible. This article focuses on the use of nanostructured materials with nanoporosity or nanotopography for ocular delivery. Specifically, we discuss nanotopography for enhanced bioadhesion and permeation and nanoporous materials for controlled release drug delivery. As examples, application of polymeric nanostructures for greater transepithelial permeability, nanostructured microparticles for enhanced preocular retention time and nanoporous membranes for tuning drug release profile are covered.

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Conflict of interest statement

Financial & competing interests disclosure This work was supported by the NIH R01-EY021574 and R01-EB018842. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Ocular structures and possible drug permeation/elimination routes.
(A) Transcorneal permeation, (B) noncorneal drug permeation, (C) drug from the blood to the anterior chamber, (D) drug elimination by aqueous humor turnover, (E) drug elimination to systemic circulation, (F) drug permeation across the blood–retinal barrier, (G) intravitreal drug administration, (H) drug elimination via blood–retinal barrier and (I) drug elimination via anterior route. Adapted with permission from [9] © Elsevier (2006).
<b>Figure 2.</b>
Figure 2.. Nanotopography-inspired approaches to enhance bioadhesion and permeation.
(A) Fluorescence images of the preocular surface of the rabbit eye after administration of particles tagged with Nile Red and scanning electron microscope (SEM) images of particles. Compared with bare PLGA or PLGA/PEG microspheres, microparticles with nanotopography achieved greater preocular retention time in vivo. White arrow indicates lower fornix of the rabbit eye and black arrow indicates the location of the eyeball. The bottom row shows SEM images of the particles. Scale bar = 5 mm for the top five rows and 20 µm for bottom row of SEM images [27]. (B) Nanostructured microneedles were fabricated by draping polymeric nanostructured film on a microneedle array. Scale bars = 300 µm and 3 µm in order [28]. (C) Nanostructures made with polypropylene or polyether ether ketone downregulate expression of tight junction proteins, such as Claudin-1 and 4, in cultured human keratinocytes as demonstrated by immunohistochemical staining. Scale bar = 10 µm [28]. PEG: Polyethylene glycol; PLGA: Poly(lactic-co-glycolic acid); PP: Polypropylene; NS: Nanostructured, PEEK: Polyether ether ketone. Adapted with permission from [27,28] © Elsevier (2014) and © American Chemical Society (2015).
<b>Figure 3.</b>
Figure 3.. SEM image of nanoporous anodized aluminum oxide membrane with pore size of 200 nm (GE Healthcare, NJ, USA).
SEM image provided by C Fox.
<b>Figure 4.</b>
Figure 4.. In vitro diffusion kinetics of fluorescein isothiocyanate-labeled bovine serum albumin through 13 nm pore size membrane under sink conditions: experimental data (o), Fick's law prediction (solid line) and model based simulation (dashed line).
FITC-BSA: Fluorescein isothiocyanate-labeled bovine serum albumin. Reproduced with permission from [60] © American Chemical Society (2004).
<b>Figure 5.</b>
Figure 5.. Example of prototypical nanoporous polycaprolactone thin film reservoir device loaded with fluorescein isothiocyanate-labeled bovine serum albumin.
Reproduced with permission from [45] © American Chemical Society (2012).
See this image and copyright information in PMC

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