Topical, aqueous, clear cyclosporine formulation design for anterior and posterior ocular delivery
Open accessAbstract
PURPOSE: The main objective of this study was to optimize cyclosporine (CsA) nanomicellar solution and study in vivo ocular CsA tissue distribution with a topical drop. METHODS: An optimized blend of hydrogenated castor oil-40 and octoxynol-40 was prepared to entrap CsA within nanomicelles. In vivo studies were conducted in New Zealand White albino rabbits with topical drop instillation. RESULTS: Average size of CsA-loaded nanomicelles was approximately 22.4 nm. Ocular tissue CsA quantification with single and multiple dosing revealed that CsA levels followed as cornea → iris-ciliary body → aqueous humor → lens. Cyclosporine levels were also found to be in the following order: conjunctiva → sclera → retina/choroid → vitreous humor. High CsA level was detected in retina/choroid (53.7 ng/g tissue). CONCLUSIONS: Ocular tissue CsA distribution studies revealed high CsA concentrations in anterior ocular tissues. Moreover, it appears that nanomicelles are transported through a conjunctival-scleral pathway and deliver CsA to the retina/choroid. Results suggest polymeric blend to be a safe carrier for anterior and posterior ocular tissues. TRANSLATIONAL RELEVANCE: This study has significant translational relevance, disclosing results that suggest that aqueous nanomicellar approach can provide high corneal and conjunctival CsA concentrations. Aqueous nanomicelles can deliver high drug concentrations not only to anterior but also to back of the eye tissues, including retina. This article provides a platform for noninvasive back of the eye drug delivery with topical eye drops. Aqueous CsA nanomicelles have no perceptible toxicity such as cell membrane damage or cytotoxicity to corneal and retinal pigment epithelial cells. Clear aqueous nanomicellar solution can be translated to human conditions for keratoconjunctivitis sicca and other anti-inflammatory conditions.
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Cholkar et al. found elevated CsA concentrations in anterior ocular tissue after topical drop instillation of CsA-loaded nanomicelles in New Zealand White albino rabbits.
“The findings revealed elevated CsA concentrations in anterior ocular tissue.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [13]
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- Authors
- Cholkar, K., Gilger, B. C., & Mitra, A. K.
- Affiliations
- University of Missouri–Kansas City (US)
- North Carolina State University (US)
- Corresponding author
- Mitra, Ashim K.
- Venue
- Translational Vision Science & Technology
- Published
- 2015-05-01
- Volume
- 4
- Issue
- 3
- Pages
- 1
- ISSN
- 2164-2591 (ISSN-L)
- PMC
- PMC4418434
- OpenAlex
- W311930526
- Cited by
- 103
- References
- 30
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 10 · 2023: 11 · 2022: 9 · 2021: 10 · 2020: 12 · 2019: 12 · 2018: 5 · 2017: 11 · 2016: 6 · 2015: 3
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Translational Vision Science & Technology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (R01EY009171, R01EY010659)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- cyclosporine, nanomicelles, ocular drug delivery, eye drops, hydrogenated castor oil, ocular tissue distribution, corneal drug concentration, dry eye, anti-inflammatory eye drops
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