Drug delivery systems and novel formulations to improve treatment of rare corneal disease

Jimenez, Jorge; Nischal, Kanwal; Fedorchak, Morgan V.

doi:10.1016/j.drudis.2019.03.005

Cited by 11 publications

(6 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unfortunately, the variable hydrophilicity of the corneal layers impacts the permeability of topical agents, while the ocular cul-de-sac limits the volume of drug solution able to be administrated and tear film turnover and lacrimation limit drug residence time. These physical and biochemical barriers are estimated to limit the bioavailability of a topically applied agent to ≤5% for some substances ( Patel et al, 2013 ; Awwad et al, 2017 ; Jimenez et al, 2019 ). Nonetheless, topical agents targeting structures posterior to the cornea, such as those used in glaucoma and non-infectious anterior uveitis treatment, demonstrate that topical drug therapy can permeate the cornea and be used for anterior segment pathologies ( Harthan et al, 2016 ; K. Schuster et al, 2020 ).…”

Section: Age-related Diseases In the Eyementioning

confidence: 99%

Potential role of extracellular granzyme B in wet age-related macular degeneration and fuchs endothelial corneal dystrophy

Dubchak

Obasanmi²,

Zeglinski³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Age-related ocular diseases are the leading cause of blindness in developed countries and constitute a sizable socioeconomic burden worldwide. Age-related macular degeneration (AMD) and Fuchs endothelial corneal dystrophy (FECD) are some of the most common age-related diseases of the retina and cornea, respectively. AMD is characterized by a breakdown of the retinal pigment epithelial monolayer, which maintains retinal homeostasis, leading to retinal degeneration, while FECD is characterized by degeneration of the corneal endothelial monolayer, which maintains corneal hydration status, leading to corneal edema. Both AMD and FECD pathogenesis are characterized by disorganized local extracellular matrix (ECM) and toxic protein deposits, with both processes linked to aberrant protease activity. Granzyme B (GrB) is a serine protease traditionally known for immune-mediated initiation of apoptosis; however, it is now recognized that GrB is expressed by a variety of immune and non-immune cells and aberrant extracellular localization of GrB substantially contributes to various age-related pathologies through dysregulated cleavage of ECM, tight junction, and adherens junction proteins. Despite growing recognition of GrB involvement in multiple age-related pathologies, its role in AMD and FECD remains poorly understood. This review summarizes the pathophysiology of, and similarities between AMD and FECD, outlines the current knowledge of the role of GrB in AMD and FECD, as well as hypothesizes putative contributions of GrB to AMD and FECD pathogenesis and highlights the therapeutic potential of pharmacologically inhibiting GrB as an adjunctive treatment for AMD and FECD.

show abstract

Section: Age-related Diseases In the Eyementioning

confidence: 99%

Potential role of extracellular granzyme B in wet age-related macular degeneration and fuchs endothelial corneal dystrophy

Dubchak

Obasanmi²,

Zeglinski³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“… 36 – 39 , 46 , 67 , 68 To achieve therapeutic concentrations in the non-vascularized cornea, however, systemically administered drugs require unacceptably high dosing. 69 High doses of tacrolimus cause significant side effects, including nephro- and hepatotoxicity 57 , 58 and sometimes neurologic 59 or psychiatric 60 symptoms, that would outweigh its anticipated benefits. Topical delivery, however, could minimize the systemic exposure while enabling a localized therapeutic drug level.…”

Section: Discussionmentioning

confidence: 99%

Sustained Release of Tacrolimus From a Topical Drug Delivery System Promotes Corneal Reinnervation

Daeschler¹,

Mirmoeini²,

Gordon

et al. 2022

Trans. Vis. Sci. Tech.

View full text Add to dashboard Cite

Purpose Corneal nerve fibers provide sensation and maintain the epithelial renewal process. Insufficient corneal innervation can cause neurotrophic keratopathy. Here, topically delivered tacrolimus is evaluated for its therapeutic potential to promote corneal reinnervation in rats. Methods A compartmentalized neuronal cell culture was used to determine the effect of locally delivered tacrolimus on sensory axon regeneration in vitro. The regenerating axons but not the cell bodies were exposed to tacrolimus (50 ng/mL), nerve growth factor (50 ng/mL), or a vehicle control. Axon area and length were measured after 48 hours. Then, a biodegradable nanofiber drug delivery system was fabricated via electrospinning of a tacrolimus-loaded polycarbonate–urethane polymer. Biocompatibility, degradation, drug biodistribution, and therapeutic effectiveness were tested in a rat model of neurotrophic keratopathy induced by stereotactic trigeminal nerve ablation. Results Sensory neurons whose axons were exposed to tacrolimus regenerated significantly more and longer axons compared to vehicle-treated cultures. Trigeminal nerve ablation in rats reliably induced corneal denervation. Four weeks after denervation, rats that had received tacrolimus topically showed similar limbal innervation but a significantly higher nerve fiber density in the center of the cornea compared to the non-treated control. Topically applied tacrolimus was detectable in the ipsilateral vitreal body, the plasma, and the ipsilateral trigeminal ganglion but not in their contralateral counterparts and vital organs after 4 weeks of topical release. Conclusions Locally delivered tacrolimus promotes axonal regeneration in vitro and corneal reinnervation in vivo with minimal systemic drug exposure. Translational Relevance Topically applied tacrolimus may provide a readily translatable approach to promote corneal reinnervation.

show abstract

“…Ocular disease treatment attracts particular interest due to the many chronic situations, such as age-related macular degeneration (AMD) and glaucoma, and the large markets for related therapeutics [11]. Moreover, because of the different anatomical and physiological berries, drug delivery for ocular tissue has continuously been challenging for drug delivery scientists and ophthalmologists.…”

Section: Methods For Cornea Drug Deliverymentioning

confidence: 99%

“…Among these barriers, there are the tear film and the cornea as physiological components. Physiological topical methods, drug loaded ocular inserts, and injection can be used for corneal drug delivery, and they are explained as below [11].…”

Section: Methods For Cornea Drug Deliverymentioning

confidence: 99%

See 1 more Smart Citation

Biodegradable Nanoparticle for Cornea Drug Delivery: Focus Review

et al. 2020

View full text Add to dashboard Cite

During recent decades, researchers all around the world have focused on the characteristic pros and cons of the different drug delivery systems for cornea tissue change for sense organs. The delivery of various drugs for cornea tissue is one of the most attractive and challenging activities for researchers in biomaterials, pharmacology, and ophthalmology. This method is so important for cornea wound healing because of the controllable release rate and enhancement in drug bioavailability. It should be noted that the delivery of various kinds of drugs into the different parts of the eye, especially the cornea, is so difficult because of the unique anatomy and various barriers in the eye. Nanoparticles are investigated to improve drug delivery systems for corneal disease. Biodegradable nanocarriers for repeated corneal drug delivery is one of the most attractive and challenging methods for corneal drug delivery because they have shown acceptable ability for this purpose. On the other hand, by using these kinds of nanoparticles, a drug could reside in various part of the cornea for longer. In this review, we summarized all approaches for corneal drug delivery with emphasis on the biodegradable nanoparticles, such as liposomes, dendrimers, polymeric nanoparticles, niosomes, microemulsions, nanosuspensions, and hydrogels. Moreover, we discuss the anatomy of the cornea at first and gene therapy at the end.

show abstract

Drug delivery systems and novel formulations to improve treatment of rare corneal disease

Cited by 11 publications

References 104 publications

Potential role of extracellular granzyme B in wet age-related macular degeneration and fuchs endothelial corneal dystrophy

Potential role of extracellular granzyme B in wet age-related macular degeneration and fuchs endothelial corneal dystrophy

Sustained Release of Tacrolimus From a Topical Drug Delivery System Promotes Corneal Reinnervation

Biodegradable Nanoparticle for Cornea Drug Delivery: Focus Review

Contact Info

Product

Resources

About