Dataset Information

Cyclosporine A eyedrops with self-nanoemulsifying drug delivery systems have improved physicochemical properties and efficacy against dry eye disease in a murine dry eye model.

ABSTRACT:

Purpose

We aimed to compare the physicochemical properties and in vivo efficacy of commercially available nanoemulsion cyclosporine A (CsA) eyedrops in benzalkonium chloride (BAC)-induced dry eye disease (DED).

Methods

Particle size analysis was performed on conventional 0.05% CsA (Restasis, C-CsA) and two new types of 0.05% CsA eyedrops based on a self-nanoemulsifying drug delivery system (SNEDDS, SNEDDS-N and -T). Turbidometry, pH measurements and instability indices of each CsA solution were measured. DED was induced with BAC, and animals were treated with vehicle or CsA preparations. Tear volume and fluorescein staining scores were evaluated on days 7 and 14. Eyes were enucleated and subjected to IHC, TUNEL staining, periodic acid-Schiff (PAS) staining, real-time PCR and western blotting.

Results

Both SNEDDSs had lower and more uniform particle size distribution than C-CsA, and a similar optical density to phosphate-buffered saline and stable pH, in contrast to the high turbidity and unstable pH of C-CsA. Aqueous tear volume and fluorescein staining scores were improved in C-CsA- and SNEDDS-treated mice. Numbers of PAS-positive goblet cells and levels of inflammatory mediators were decreased by both C-CsA and SNEDDS, although SNEDDS resolved inflammation more effectively than C-CsA.

Conclusions

Cyclosporine A eyedrops with SNEDDS have improved physicochemical properties and treatment efficacy in BAC-induced DED.

SUBMITTER: Bang SP

PROVIDER: S-EPMC6860930 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Cyclosporine A eyedrops with self-nanoemulsifying drug delivery systems have improved physicochemical properties and efficacy against dry eye disease in a murine dry eye model.

Bang Seung Pil SP Yeon Chang Yeor CY Adhikari Nirpesh N Neupane Sanjiv S Kim Harim H Lee Dong Cheol DC Son Myeong Jin MJ Lee Hyun Gyo HG Kim Jae-Young JY Jun Jong Hwa JH

PloS one 20191118 11

<h4>Purpose</h4>We aimed to compare the physicochemical properties and in vivo efficacy of commercially available nanoemulsion cyclosporine A (CsA) eyedrops in benzalkonium chloride (BAC)-induced dry eye disease (DED).<h4>Methods</h4>Particle size analysis was performed on conventional 0.05% CsA (Restasis, C-CsA) and two new types of 0.05% CsA eyedrops based on a self-nanoemulsifying drug delivery system (SNEDDS, SNEDDS-N and -T). Turbidometry, pH measurements and instability indices of each CsA ...[more]

PMID: 31738791

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Project description:ImportanceDry eye disease (DED) is a prevalent eye disorder. Cyclosporine is an effective immunomodulator that is widely used in DED; however, due to its highly hydrophobic nature, delivery of cyclosporine to the ocular surface is challenging.ObjectiveTo evaluate the efficacy and safety of SHR8028, a water-free cyclosporine ophthalmic solution, 0.1%, compared with vehicle in Chinese participants with DED.Design, setting, and participantsThis was a multicenter, double-blind, vehicle-controlled, phase 3 randomized clinical trial conducted from March 4, 2021, to July 22, 2022. Adult participants with moderate to severe DED were recruited from 12 hospitals in China. Study data were analyzed April 2, 2022, for the primary analysis.InterventionsFollowing a 14-day run-in period with an artificial tear, participants were randomly assigned (1:1) to receive water-free cyclosporine or vehicle (1 eye drop in each eye twice daily). After a 29-day treatment, participants of both groups were given the option to receive water-free cyclosporine for an additional 12 weeks for longer-term safety assessment.Main outcomes and measuresThe primary end points were changes from baseline in total corneal fluorescein staining (tCFS) using the National Eye Institute scale and in dryness score on a visual analog scale at day 29.ResultsA total of 206 participants (mean [SD] age, 47.8 [14.2] years; 185 female [90%]) were enrolled, with 103 each in the cyclosporine group and the vehicle group. At day 29, the cyclosporine group experienced improved tCFS compared with vehicle (change [Δ] = -1.8; 95% CI, -2.7 to -1.0; P < .001), with a tCFS score decrease from baseline of -4.8 in the cyclosporine group and -3.0 in the vehicle group. Dryness score decreased from baseline in both groups (-19.2 vs -15.4; Δ = -3.8; 95% CI, -9.2 to 1.6; P = .17). During the 29-day treatment, treatment-related adverse events were reported in 15 participants (14.6%) in the cyclosporine group and 11 participants (10.7%) in the vehicle group.Conclusions and relevanceResults demonstrated superiority of a water-free cyclosporine, 0.1%, eye solution over vehicle in improving tCFS score at day 29 in Chinese participants with DED. However, dryness score (VAS) was not improved at day 29.Trial registrationClinicalTrials.gov Identifier: NCT05841043.

Dataset Information

Cyclosporine A eyedrops with self-nanoemulsifying drug delivery systems have improved physicochemical properties and efficacy against dry eye disease in a murine dry eye model.

Purpose

Methods

Results

Conclusions

Publications

Cyclosporine A eyedrops with self-nanoemulsifying drug delivery systems have improved physicochemical properties and efficacy against dry eye disease in a murine dry eye model.

Similar Datasets

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