A self-healing hydrogel eye drop for the sustained delivery of decorin to prevent corneal scarring

Chouhan, Gurpreet; Moakes, Richard J. A.; Esmaeili, Maryam; Hill, Lisa J; Felicity, Decogan; Hardwicke, Joseph; Rauz, Saaeha; Logan, Ann; Grover, Liam M.

doi:10.1016/j.biomaterials.2019.04.013

Cited by 53 publications

(26 citation statements)

References 53 publications

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“…Decorin fluid gels and fluid gels (without decorin) were produced using low acyl gellan gum (Kelco gel CG LA, Azelis, UK) as previously described [46]. The fluid gels were used to provide localised drug delivery and improved retention on the ocular surface [37].…”

Section: Preparation Of Decorin Decorin Fluid Gel and Fluid Gel Eye mentioning

confidence: 99%

The neuroregenerative effects of topical decorin on the injured mouse cornea

Downie

Grover

et al. 2020

J Neuroinflammation

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Background: The cornea is innervated with a rich supply of sensory nerves that play important roles in ocular surface health. Any injury or pathology of the corneal nerves increases the risk of dry eye disease and infection. This study aims to evaluate the therapeutic potential of topical decorin to improve corneal nerve regeneration in a mouse model of sterile epithelial abrasion injury. Methods: Bilateral central corneal epithelial abrasions (2-mm, Alger Brush) were performed on young C57BL/6 J mice to remove the corneal sensory nerves. Decorin, or vehicle, was applied topically, three times per day for 1 week or every 2 h for 6 h. Spectral-domain optical coherence tomography was performed to measure the abrasion area and corneal thickness. Wholemount immunofluorescence staining was used to assess sensory nerve regeneration (β-tubulin III) and immune cell density (CD45, Iba1, CD11c). To investigate the specific role of dendritic cells (DCs), Cx3cr1 gfp/gfp mice, which spontaneously lack resident corneal epithelial DCs, were also investigated. The effect of prophylactic topical administration of recombinant human decorin (applied prior to the abrasion) was also investigated. Nerve tracing (NeuronJ software) was performed to compare recovery of basal nerve axons and superficial nerve terminals in the central and peripheral cornea. Results: At 6 h after injury, topical decorin application was associated with greater intraepithelial DC recruitment but no change in re-epithelialisation or corneal thickness, compared to the vehicle control. One week after injury, sub-basal nerve plexus and superficial nerve terminal density were significantly higher in the central cornea in the decorin-treated eyes. The density of corneal stromal macrophages in the decorin-treated eyes and their contralateral eyes was significantly lower compared to saline-treated corneas. No significant improvement in corneal nerve regeneration was observed in Cx3cr1 gfp/gfp mice treated with decorin. Conclusions: Decorin promotes corneal epithelial nerve regeneration after injury. The neuroregenerative effect of topical decorin was associated with a higher corneal DC density during the acute phase, and fewer macrophages at the study endpoint. The corneal neuroregenerative effects of decorin were absent in mice lacking intraepithelial DCs. Together, these findings support a role for decorin in DC-mediated neuroregeneration following corneal abrasion injury.

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Section: Preparation Of Decorin Decorin Fluid Gel and Fluid Gel Eye mentioning

confidence: 99%

The neuroregenerative effects of topical decorin on the injured mouse cornea

Downie

Grover

et al. 2020

J Neuroinflammation

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“…A very interesting solution is the idea of Chouhan et al concerning the hydrogel eye drop as a carrier providing and maintaining medicines on the eye surface. In these studies, the use of gellan fluid gel to ensure a continuous supply of drugs was presented [ 8 ]. Another important solution was reported by Tamahkar et al, who presented multilayer hydrogel dressings.…”

Section: Introductionmentioning

confidence: 99%

Physicochemical Investigations of Chitosan-Based Hydrogels Containing Aloe Vera Designed for Biomedical Use

et al. 2020

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In this work, synthesis and investigations on chitosan-based hydrogels modified with Aloe vera juice are presented. These materials were synthesized by UV radiation. Investigations involved analysis of chemical structure by FTIR spectroscopy, sorption properties in physiological liquids, strength properties by texture analyzer, surface topography by Atomic Force Microscopy (AFM technique), and in vitro cytotoxicity by MTT test using L929 murine fibroblasts. Particular attention was focused both on determining the impact of the amount and the molecular weight of the crosslinker used for the synthesis as well as on the introduced additive on the properties of hydrogels. It was proven that modified hydrogels exhibited higher swelling ability. Introduced additive affected the tensile strength of hydrogels—modified materials showed 23% higher elongation. The greater amount of the crosslinker used in the synthesis, the more compact the structure, leading to the lower elasticity and lower sorption of hydrogels was reported. Above 95%, murine fibroblasts remained viable after 24 h incubation with hydrogels. It indicates that tested materials did not exhibit cytotoxicity toward these lines. Additionally, materials with Aloe vera juice were characterized by lower surface roughness. Conducted investigations allowed us to state that such modified hydrogels may be considered as useful for biomedical purposes.

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“…Fluid gels have been explored as a versatile deviation from the traditional hydrogel structure and are formed by shearing hydrogel to produce a complex hydrogel microstructure as opposed to a macrostructure 61. Fluid gels therefore retain the viscosity and favorable drug delivery profile of a gel, while allowing for the necessary flow characteristics for spraying, pouring, and drop formation, and they present as a promising medium for eye drops 61,110,111. The level of shearing the ‘gel' is exposed to also ‘controls' the microstructure, which in turn can control the spreadability of the drop.…”

Section: Innovations In Topical Ocular Drug Deliverymentioning

confidence: 99%

“…Although tailoring mucoadhesive polymers presents one option for improving the efficacy of eye drops, other avenues are also being explored, including emulsions and microemulsions, lipid‐based carriers, and permeation enhancers 63c,111b,117. Lipid or emulsion‐based eye drops show comparable results to conventional polymer‐based drops 117,118.…”

Section: Innovations In Topical Ocular Drug Deliverymentioning

confidence: 99%

Material, Immunological, and Practical Perspectives on Eye Drop Formulation

Bennett

Chinnery

Downie

et al. 2020

Adv Funct Materials

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Eye drops are the most common and inexpensive approach to topical ocular drug delivery. Eye drops offer a noninvasive treatment strategy; however, this can be detrimental to therapeutic efficacy when compared to invasive methods such as surgeries, implants, and injections. Improvements to the efficacy of the topical delivery of drugs to ocular tissues are currently being explored and much of this work centers on adjusting the formulation of the eye drops and prolonging the bioavailability of the therapeutic agent. This is often in preference to improving other patient‐focused or clinical factors. In this progress report, conventional, commercially available polymer eye drops are explored and the ability for current and future innovations to maintain the existing benefits of eye drops to the patient is assessed. The final materials and form of the drops (liquid, gel, or other) and the immunological implications for the user are explored. There is currently no consensus for how to most effectively improve the ocular retention and drug delivery capabilities of eye drops, but key issues are highlighted in the context of current methods under development, and potential questions and considerations for future innovations are raised.

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A self-healing hydrogel eye drop for the sustained delivery of decorin to prevent corneal scarring

Cited by 53 publications

References 53 publications

The neuroregenerative effects of topical decorin on the injured mouse cornea

The neuroregenerative effects of topical decorin on the injured mouse cornea

Physicochemical Investigations of Chitosan-Based Hydrogels Containing Aloe Vera Designed for Biomedical Use

Material, Immunological, and Practical Perspectives on Eye Drop Formulation

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