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Review
. 2014 Apr 28;55(4):2714-30.
doi: 10.1167/iovs.13-13707.

Drug and gene delivery to the back of the eye: from bench to bedside

Cheryl L Rowe-Rendleman  1 , Shelley A Durazo, Uday B Kompella, Kay D Rittenhouse, Adriana Di Polo, Alan L Weiner, Hans E Grossniklaus, Muna I Naash, Alfred S Lewin, Alan Horsager, Henry F Edelhauser
Affiliations
Review

Drug and gene delivery to the back of the eye: from bench to bedside

Cheryl L Rowe-Rendleman et al. Invest Ophthalmol Vis Sci. .
No abstract available

Keywords: drug delivery; gene therapy; nanoparticle; retina; translational medicine.

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Figures

Figure 1
Figure 1
Innovations for topical drugs that are intended to treat diseases in the back of the eye. Eye drops are one of several drug delivery vehicles that can be modified to deliver medical therapy to the back of the eye. Limitations of some suspensions and solutions include low solubility, poor permeation of the ocular surface and short retention time in the eye. Solutions of polyguanidilyated dendrimers form nano-sized complexes with drugs to enhance their solubility, permeability, and retention. In vitro studies showed that 6-guanyl dendrimeric formulation of gatifloxacin increased the solubility of the antibiotic by 4-fold, increased its transport across a preparation of bovine sclera-choroid-RPE, and enhanced its uptake by human corneal epithelial cells. HDNP may also be used to increase the residence time of drugs on the ocular surface. Animal studies indicated that a hydrogel and dendrimer formulation of two topical antiglaucoma drugs extended the duration of IOP lowering for 4 days in rabbits.
Figure 2
Figure 2
Intraocular drug delivery bypasses anatomic and dynamic barriers of the posterior segment. The placement of a therapeutic substance directly into the vitreous (intravitreal injection) or the space between the retina and the RPE (subretinal injection) though invasive, achieves the highest intraocular bioavailability by bypassing several anatomic and dynamic barriers of the posterior segment. However there is much to be learned about the dynamic mechanisms that clear these drugs from the ocular spaces and subsequently, frequent injections are needed to maintain the therapeutic effect of small molecules and proteins. Attachment of PEGylated complexes to proteins to extend their viability in the vitreous has been explored in preclinical models, although the complexes have many of the same physical properties as the non-PEGylated native protein, more work is needed to determine if the modified molecules can find their targets in vivo. Direct subretinal injection of self-assembling nonviral DNA nanoparticles carrying the mouse opsin promoter and wild type mouse Rds gene has shown promise in rescuing a mouse model of retinitis pigmentosa.
Figure 3
Figure 3
Subconjunctival placement of hydrogels for periocular drug delivery. Periocular drug delivery methods exploit the trans-scleral routes for delivery of drugs to the retina. Hydrogels are biocompatible, thermoresponsive polymers that can be cured by UV light. Hydrogel formulations are variable and can be made from polylactic coglycolic acid and PEG; poly (NIPA Am-co-Dex-lactate HEMA) or other combinations which gives them efficient loading capacities and the capability to encapsulate and control the release of a variety of drugs. Proof of concept has been explored with small peptides like insulin.
Figure 4
Figure 4
Drug delivery to the suprachoroidal space with microneedles. Microneedle injection is a special type of trans-scleral drug delivery to the suprachoroidal space. The tip end of the microneedle is inserted through the sclera and the formulation is injected once the needle reaches the end of sclera. The formulation flows circumferentially while filling the suprachoroidal space toward the retinochoroidal tissue, macula, and optic nerve in the posterior segment of the eye. Low-magnification view of a microneedle at the end of a syringe (A) and high-magnification comparison of a microneedle (left) to the tip of a 30-gauge hypodermic needle (right) (B). Scale bars: 5 mm (A) and 500 μm (B). Top-right image reprinted with permission from Patel SR, Berezovsky DE, McCarey BE, Zarnitsyn V, Edelhauser HF, Prausnitz MR. Targeted administration into the suprachoroidal space using a microneedle for drug delivery to the posterior segment of the eye. Invest Ophthalmol Vis Sci. 2013;54:4433–4441. Copyright 2013 ARVO.
Figure 5
Figure 5
Intravenous injection of drugs for delivery to the back of the eye. Delivery of drugs to the back of the eye from the systemic circulation is impeded by the inner and outer blood retinal barriers. In animal models, nanoparticles that have been functionalized with RGD and transferrin appear able to breech these barriers and reach the back of the eye and neovascular endothelial cells in an experimental model of choroidal neovascularization in rats. If functionalized nanoparticles appear safe and well-localized upon extensive tests in various animal models, it may ultimately replace other more invasive methods of intraocular drug delivery.
See this image and copyright information in PMC

References

    1. Edelhauser HF, Rowe-Rendleman CL, Robinson MR, et al. Ophthalmic drug delivery systems for the treatment of retinal diseases: basic research to clinical applications. Invest Ophthalmol Vis Sci. 2010; 51: 5403–5420 - PMC - PubMed
    1. Gordois A, Pezzullo L, Cutler H. The Global Economic Cost of Visual Impairment. Sidney: Access Economics Pty Limited; 2010.
    1. Sebag J. Age-related changes in human vitreous structure. Graefes Arch Clin Exp Ophthalmol. 1987; 225: 89–93 - PubMed
    1. Hughes PM, Olejnik O, Chang-Lin JE, Wilson CG. Topical and systemic drug delivery to the posterior segment. Adv Drug Deliv Rev. 2005; 57: 2010–2032 - PubMed
    1. Bill A. Movement of albumin and dextran through the sclera. Arch Ophthalmol. 1965; 74: 248–252 - PubMed

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