Therapeutic interventions for herpes simplex virus epithelial keratitis

Wilhelmus, Kirk R.

doi:10.1002/14651858.cd002898.pub3

Cited by 31 publications

(25 citation statements)

References 121 publications

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“…For example, treatment of herpetic keratitis requires nine drops a day of trifluridine or intraocular pressure lowering regimens to treat advanced glaucoma require multiple complex drug dosing [27,28]. In areas of experimental eye research, modulating the ocular surface with growth factors may also require multiple dosing regimens.…”

Section: Discussionmentioning

confidence: 99%

Biodegradable PLGA-Based Drug Delivery Systems for Modulating Ocular Surface Disease under Experimental Murine Dry Eye

Chang¹,

McClellan²,

Farley³

et al. 2011

J Clinic Experiment Ophthalmol

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Objective Continuous drug delivery to the ocular surface remains difficult due to the rapid tear clearance of topically applied agents. The purpose of this study was to evaluate biodegradable and biocompatible drug delivery systems on the ocular surface using poly-lactic-co-glycolic acid (PLGA) based polymers. Methods Fluorescein-labeled albumin and doxycycline were individually encapsulated into a PLGA-based matrix using a water-oil-water double emulsion method. The drug elution rates for various microspheres were evaluated spectrofluorometrically. Particle size was measured using image analysis software. Subconjunctival injections of PLGA microspheres were used to evaluate safety and inflammatory response to the polymer in the murine model. Efficacy of the drug delivery system was evaluated by a single subconjunctival injection of PLGA-doxycycline (a broad metalloproteinase inhibitor) prior to induction of desiccating stress (DS) model in C57BL/6 mice for 5 days. Results PLGA-based microspheres successfully elute encapsulated drugs of interest continuously over controlled periods of time. Mean PLGA-based microparticle diameter was 4.6 μm±1.54 μm. Drug elution rates and delivery times were easily modifiable by altering polymers and synthesis parameters. In vitro studies demonstrate successful continuous elution of encapsulated drugs for at least 2 weeks. In vivo testing of PLGA-doxycycline was efficacious in preventing DS-induced corneal barrier disruption with desiccating stress, similarly to topically applied doxycycline. Conclusions PLGA-based drug delivery systems are safe and non-inflammatory. They can be successfully used to treat ocular surface and corneal diseases by continuously delivering biopharmaceuticals of interest.

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Section: Discussionmentioning

confidence: 99%

Biodegradable PLGA-Based Drug Delivery Systems for Modulating Ocular Surface Disease under Experimental Murine Dry Eye

Chang¹,

McClellan²,

Farley³

et al. 2011

J Clinic Experiment Ophthalmol

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“…Topical application with nucleoside analogues including vidarabine, trifluridine, ACV or ganciclovir results in healing, usually within 1 week. Interferon may be effective when combined with another antiviral agent, such as trifluridine [6]. Recurrences are common, and suppressive oral ACV or VCV therapy may be beneficial, and reduce the rate of recurrent HSV epithelial keratitis and stromal keratitis [7].…”

Section: Clinical Syndromes and Current Treatmentmentioning

confidence: 99%

Novel approaches in fighting herpes simplex virus infections

Wilson¹,

Fakioglu²,

Herold³

2009

Expert Review of Anti-infective Therapy

101

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The development of novel strategies to eradicate herpes simplex virus (HSV) is a global public health priority. While acyclovir and related nucleoside analogues provide successful modalities for treatment and suppression, HSV remains highly prevalent worldwide and is a major cofactor fueling the HIV epidemic. HSV is the predominant cause of genital ulcerative disease, and neonatal and sporadic infectious encephalitis. Asymptomatic shedding, which occurs more frequently than previously appreciated, contributes to viral transmission. Acyclovir resistance may be problematic for immunocompromised patients and highlights the need for new safe and effective agents. Ideally, vaccines to prevent infection, drugs to inhibit the establishment of or reactivation from latency, or vaginal microbicides to prevent sexual and perinatal transmission are needed to control the epidemic. This review summarizes current therapeutic options and strategies in development. Keywords acyclovir; herpes simplex virus; microbicide; vaccineThe discovery of acyclovir (ACV), a nucleoside analogue that is selectively phosphorylated by herpes simplex virus (HSV) and inhibits viral replication by acting as a substrate for viral DNA polymerase, ushered in a new era in antiviral chemo therapy [1,2]. Despite the overwhelming success of ACV and related drugs, HSV remains a major global health problem, and is the leading cause of encephalitis and genital ulcerative disease, and a major cofactor for HIV infection. This reflects, in part, the ability of the virus to uniformly establish latency, reactivate frequently and to be horizontally and vertically transmitted during periods of

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“…Topical trifluridine, vidarabine, idoxuridine and acyclovir (ACV) are currently employed in the treatment of epithelial keratitis(4, 5). ACV is a hydrophilic antiviral nucleoside analog that is extremely effective against HSV-1 induced corneal keratitis(6). ACV cannot be formulated as eye drops, since it has a saturation solubility of 1.2 mg/mL in water, and is thus marketed as a 3% ointment(7).…”

Section: Introductionmentioning

confidence: 99%

Transcorneal Permeation of l- and d-Aspartate Ester Prodrugs of Acyclovir: Delineation of Passive Diffusion Versus Transporter Involvement

et al. 2008

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Purpose-The aim of this study was to evaluate the contribution of amino acid transporters in the transcorneal permeation of the aspartate (Asp) ester acyclovir (ACV) prodrug.Methods-Physicochemical characterization, solubility and stability of acyclovir L-aspartate (LAsp-ACV) and acyclovir D-aspartate (D-Asp-ACV) were studied. Transcorneal permeability was evaluated across excised rabbit cornea.Results-Solubility of L-Asp-ACV and D-Asp-ACV were about 2-fold higher than that of ACV. The prodrugs demonstrated greater stability under acidic conditions. Calculated pK a and logP values for both prodrugs were identical. Transcorneal permeability of L-Asp-ACV (12.1±1.48×10 −6 cm/s) was 4-fold higher than D-Asp-ACV (3.12±0.36×10 −6 cm/s) and ACV (3.25±0.56×10 −6 cm/s). ACV generation during the transport process was minimal. L-Asp-ACV transport was sodium and energy dependent but was not inhibited by glutamic acid. Addition of BCH, a specific B o,+ and L amino acid transporter inhibitor, decreased transcorneal L-Asp-ACV permeability to 2.66±0.21×10 −6 cm/ s. L-Asp-ACV and D-Asp-ACV did not demonstrate significant difference in stability in ocular tissue homogenates.Conclusion-The results demonstrate that enhanced transport of L-Asp-ACV is as a result of corneal transporter involvement (probably amino acid transporter B 0,+ ) and not as a result of changes in physicochemical properties due to prodrug derivatization (permeability of D-Asp-ACV and ACV were not significantly different).

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Therapeutic interventions for herpes simplex virus epithelial keratitis

Cited by 31 publications

References 121 publications

Biodegradable PLGA-Based Drug Delivery Systems for Modulating Ocular Surface Disease under Experimental Murine Dry Eye

Biodegradable PLGA-Based Drug Delivery Systems for Modulating Ocular Surface Disease under Experimental Murine Dry Eye

Novel approaches in fighting herpes simplex virus infections

Transcorneal Permeation of l- and d-Aspartate Ester Prodrugs of Acyclovir: Delineation of Passive Diffusion Versus Transporter Involvement

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