Diffusion across the sclera

Maurice, David M.; Polgár, J.

doi:10.1016/0014-4835(77)90136-1

Cited by 118 publications

(60 citation statements)

References 6 publications

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“…Thus, the ideal location for transscleral drug delivery is near the equator at 12-17 mm posterior to the corneoscleral limbus [25]. Hydrophobicity of drugs affects scleral permeability; increase of lipophilicity shows lower permeability; and hydrophilic drugs may diffuse through the aqueous medium of proteoglycans in the fiber matrix pores more easily than lipophilic drugs [26,27].…”

Section: Scleramentioning

confidence: 99%

Recent Advances in Ocular Drug Delivery Systems

2011

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Abstract:Transport of drugs applied by traditional dosage forms is restricted to the eye, and therapeutic drug concentrations in the target tissues are not maintained for a long duration since the eyes are protected by a unique anatomy and physiology. For the treatment of the anterior segment of the eye, various droppable products to prolong the retention time on the ocular surface have been introduced in the market. On the other hand, direct intravitreal implants, using biodegradable or non-biodegradable polymer technology, have been widely investigated for the treatment of chronic vitreoretinal diseases. There is urgent need to develop ocular drug delivery systems which provide controlled release for the treatment of chronic diseases, and increase patient's and doctor's convenience to reduce the dosing frequency and invasive treatment. In this article, progress of ocular drug delivery systems under clinical trials and in late experimental stage is reviewed.

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Section: Scleramentioning

confidence: 99%

Recent Advances in Ocular Drug Delivery Systems

2011

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“…Several authors have shown that scleral permeability declines with an increasing MWT, 6,7,8,21 but others have postulated that molecular radius is a better predictor of permeability. 8 It has been reported that the globular protein albumin, with a MWT of 69 kDa and radius of 3.5 nm, has higher scleral permeability than a linear dextran of 40 kDa and 4.5 nm radius.…”

Section: Effect Of Molecular Size and Shape On Scleral Permeabilitymentioning

confidence: 99%

“…33,50 Notwithstanding these potential difficulties, transscleral delivery has a number of potential advantages. 6,7,8,9 The sclera has a large and accessible surface area, and a high degree of hydration, making it conducive to water-soluble substances. It is also hypocellular and thus the proteolytic enzymes are less likely to degrade drugs.…”

Section: Introductionmentioning

confidence: 99%

Influence of molecular shape, conformability, net surface charge, and tissue interaction on transscleral macromolecular diffusion

Srikantha

Mourad

Suhling

et al. 2012

Experimental Eye Research

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Purpose: To study the influence of molecular shape, conformability, net surface charge and tissue interaction on transscleral diffusion.Methods: Unfixed, porcine sclera was clamped in an Ussing chamber. Fluorophore labelled, neutral, albumin, dextran, or ficoll were placed in one hemi-chamber and the rate of transscleral diffusion was measured over 24 hours using a spectrophotometer. Experiments were repeated using dextrans and ficoll with positive, or negative, net surface charges.Fluorescence recovery after photobleaching (FRAP) was undertaken to compare transscleral diffusion with diffusion through a solution.All molecules were 70 kDa.Results: Using FRAP, mean ± SD diffusion coefficient (D) was highest for albumin, followed by ficoll, then dextran (p = 0.0005). Positive dextrans diffused fastest, followed by negative, then neutral dextrans (p = 0.0005). Neutral ficoll diffused the fastest, followed by positive then negative ficoll (p = 0.0008). For the neutral molecules, transscleral D was highest for albumin, followed by dextran, then ficoll (p < 0.0001). D was highest for negative ficoll, followed by neutral, then positive ficoll (p < 0.0001). By contrast, D was highest for positive dextran, followed by neutral, then negative dextran (p = 0.0021).Conclusions: Diffusion in free solution does not predict transscleral diffusion and the molecular-tissue interaction is important. Molecular size, shape, and charge may all markedly influence transscleral diffusion, as may conformability to a lesser degree, but all need to be considered when selecting or designing drugs for transscleral delivery.Drugs directed against vascular endothelial growth factor (VEGF) have proven efficacy in some of the most common retinal diseases. The ANCHOR and MARINA studies demonstrated efficacy in wet age-related macular degeneration (AMD), 1,2 and studies such as CRUISE, BRAVO 3,4 and several from the DRCnet Group have shown favourable results in retinal vein occlusion and diabetic macular oedema. Whilst the data in these studies have led to improved clinical care, the need for regular intravitreal injections represents a burdensome regimen of treatment. A less invasive mode of delivery would have potential advantages in terms of reduced cost, discomfort, and complication rate.Systemic administration is impeded by the blood-aqueous and blood-retinal-barriers. High drug concentrations may be required to overcome these barriers to diffusion, with the attendant risk of systemic side effects. 5 A topical route would have obvious advantages. Delivery to the retina is however difficult for several reasons, such as lacrimation, low corneal permeability to large molecules, counter directional intraocular convection, and importantly the long diffusional distance. 53 Blood flow in the conjunctiva, episclera and choroid can also reduce drug concentration. 33,50 Notwithstanding these potential difficulties, transscleral delivery has a number of potential advantages. 6,7,8,9 The sclera has a large and accessible surface area, and a high d...

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“…Hydrophilic compounds may diffuse through the aqueous media of proteoglycans in the fiber matrix pores more easily than lipophilic compounds [36] . Solutes with negative charges have been found to have higher permeabilities than those with positive charges in bovine and porcine sclera [35,45] . Proteoglycans in the sclera are negatively charged [46] , which may contribute to the binding of positively charged molecules.…”

Section: Scleramentioning

confidence: 99%

“…Rabbits that received a sub-Tenon's injection of triamcinolone acetonide with an incised 'conjunctival window' created to inhibit local blood and lymphatic clearance in the conjunctiva had higher levels of drug in the vitreous than rabbits that did not have the incision [74] . [38,40] Decrease with increasing molecular weight [62] Exponential decrease with increasing molecular radius [53] Lipophilicity Decrease with increase in lipophilicity [35,36,44] Decrease with increase in lipophilicity [35] Increase with increase in lipophilicity [53] Charge Increase with negatively charged solutes [35,45] Increase with negatively charged solutes [35] Not studied Experiments were also performed to compare the delivery of sodium fluorescein to the retina by periocular injection and a unidirectional episcleral exoplant. The exoplant allowed release of dye on the episcleral side but not on the conjunctival side.…”

Section: Conjunctival/episcleral Clearancementioning

confidence: 99%

Transport Barriers in Transscleral Drug Delivery for Retinal Diseases

et al. 2007

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Transscleral delivery has emerged as an attractive method for treating retinal disorders because it offers localized delivery of drugs as a less invasive method compared to intravitreal administration. Numerous novel transscleral drug delivery systems ranging from microparticles to implants have been reported. However, transscleral delivery is currently not as clinically effective as intravitreal delivery in the treatment of retinal diseases. Transscleral drug delivery systems require drugs to permeate through several layers of ocular tissue (sclera, Bruch’s membrane-choroid, retinal pigment epithelium) to reach the neuroretina. As a result, a steep drug concentration gradient from the sclera to the retina is established, and very low concentrations of drug are detected in the retina. This steep gradient is created by the barriers to transport that hinder drug molecules from successfully reaching the retina. A review of the literature reveals 3 types of barriers hindering transscleral drug delivery: static, dynamic and metabolic. While static barriers have been examined in detail, the literature on dynamic and metabolic barriers is lacking. These barriers must be investigated further to gain a more complete understanding of the transport barriers involved in transscleral drug delivery.

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Diffusion across the sclera

Cited by 118 publications

References 6 publications

Recent Advances in Ocular Drug Delivery Systems

Recent Advances in Ocular Drug Delivery Systems

Influence of molecular shape, conformability, net surface charge, and tissue interaction on transscleral macromolecular diffusion

Transport Barriers in Transscleral Drug Delivery for Retinal Diseases

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