Ocular distribution of cyclosporine following topical administration of OTX-101 in New Zealand white rabbits
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Abstract Purpose: Evaluate the ocular distribution, tolerability, and systemic exposure of cyclosporine (CsA) in New Zealand white rabbits following topical administration of OTX-101, a novel, clear aqueous nanomicellar solution developed for the treatment of dry eye disease (DED). Methods: The study design included single- and repeat-dose phases. In the single-dose phase, rabbits received a single instillation of OTX-101 0.05% or CsA ophthalmic emulsion 0.05% (Restasis ® ; Allergan, Irvine, CA) as a comparator. In the repeat-dosing phase, OTX-101 (0.01%, 0.05%, or 0.1% CsA) or comparator was instilled 4 times per day for 7 days. Samples collected included whole blood, tears, and ocular tissues/fluids (aqueous humor, choroid-retina, conjunctiva, cornea, superior eyelid, third eyelid, iris/ciliary body, lacrimal gland, lens, sclera, and vitreous humor). CsA concentrations were analyzed using liquid chromatography-tandem mass spectrometry. Results: Analysis included samples from 112 rabbits. The highest concentration of CsA following a single OTX-101 0.05% instillation occurred in the third eyelid (C max = 1,200 ng/g). Concentrations of CsA in the cornea and superior bulbar conjunctiva increased in a dose-related manner following repeated administration of OTX-101 formulations; C max [T max (h)] for cornea was 1,543 ng/g (6.50), 5,410 ng/g (7.0), and 8,123 ng/g (6.50), for 0.01%, 0.05%, and 0.1% CsA concentrations, respectively; for superior bulbar conjunctiva was 726 ng/g (6.50), 1,468 ng/g (6.50), and 2,080 ng/g (6.25), respectively. Conclusions: OTX-101 topical ophthalmic instillation resulted in extensive distribution of CsA in ocular tissues, particularly in target tissues for DED (cornea and conjunctiva), while systemic exposure was negligible.
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OTX-101 nanomicellar solution resulted in dose-dependent accumulation of CsA in corneal tissue and superior bulbar conjunctiva.
“It has been found that concentrations of CsA in corneal tissue and superior bulbar conjunctiva accumulated in a dose-dependent manner [124,125].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [124]
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From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics
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“It has been found that concentrations of CsA in corneal tissue and superior bulbar conjunctiva accumulated in a dose-dependent manner [124,125].”
- Authors
- Weiss, S. L., & Kramer, W. G.
- Affiliations
- Auven Therapeutics (United States) (US)
- Kramer Consulting LLC, North Potomac, Maryland.
- Corresponding author
- Weiss, Sidney L.
- Venue
- Journal of Ocular Pharmacology and Therapeutics
- Publisher
- SAGE Publications
- Published
- 2019-09-01
- Volume
- 35
- Issue
- 7
- Pages
- 395-402
- ISSN
- 1080-7683 (ISSN-L)
- 1557-7732
- PMC
- PMC6735319
- OpenAlex
- W2915293434
- Cited by
- 41
- References
- 14
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 2 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 4
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Ocular Pharmacology and Therapeutics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Investigative Ophthalmology & Visual Science
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Keywords
- cyclosporine, dry eye, ocular drug distribution, topical ocular administration, cornea, conjunctiva, third eyelid, aqueous humor, vitreous humor, lacrimal gland, systemic exposure, tolerability, rabbits, dose-response relationship
- MeSH terms
- Animals, Chromatography, Liquid, Dose-Response Relationship, Drug, Eye, Female, Immunosuppressive Agents, Micelles, Rabbits, Tissue Distribution, Cyclosporine, Tandem Mass Spectrometry, Nanoparticles, Administration, Ophthalmic
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