Overcoming the anatomical and physiological barriers in topical eye surface medication using a peptide-decorated polymeric micelle
Abstract
The sealed anatomical features of the eye and its physiological activity that rapidly removes drugs are called anatomical and physiological barriers, which are the cause of more than 90% of drug loss. This aspect remains a critical issue in eye surface medication. Thus, promoting tissue permeability of drugs as well as prolonging their retention on the eye surface can improve their bioavailability and enhance their therapeutic effects. Thanks to the existence of a negatively charged mucin layer on the eye surface, several peptide-decorated polymeric micelles were prepared to enhance the interaction between the micelle and eye surface, thus prolonging the drug retention on the eye surface and promoting its tissue permeability. Tacrolimus (also known as FK506) is a hydrophobic macrolide immunosuppressant used to treat dry eye syndrome and other eye diseases. However, its hydrophobic nature makes its delivery as a topical eye surface medication difficult, with the risk of side effects due to overdoses. Therefore, the aim of this work is to evaluate the ability of FK506 micelles in promoting their permeability on the eye surface. Our results showed that the positively charged nanomicelles could significantly prolong FK506 retention on the eye surface and enhance its corneal permeability in ex vivo and in vivo conditions. FK506 nanomicelles exhibited superior curing effects against dry eye diseases than the FK506 suspension and a commercial FK506 formula. It exerted better inhibitory effects on eye surface inflammation and corneal epithelium apoptosis when examined by a slip lamp and a transferase-mediated dUTP nick end labeling assay, respectively. Further assays revealed the higher suppressive effects on the expression of several inflammation-related factors at an mRNA and protein level. Hence, our results suggested that these positively charged nanomicelles might be a good drug delivery system for ocular surface medication.
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Lin et al. found that positively charged nanomicelles significantly prolong tacrolimus retention on the ocular surface and enhance corneal permeability under ex vivo and in vivo conditions, yielding superior inhibitory effects on ocular surface inflammation and corneal epithelial apoptosis.
“Results showed that the positively charged nanomicelles could significantly prolong the tacrolimus retention on ocular surface and enhance its corneal permeability under ex vivo and in vivo conditions.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [19]
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- Authors
- Lin, S., Ge, C., Wang, D., Xie, Q., Wu, B., Wang, J., Nan, K., Zheng, Q., & Chen, W.
- Affiliations
- Wenzhou Institute, University of Chinese Academy of Sciences (CN)
- Wenzhou Medical University (CN)
- Corresponding author
- Nan, Kaihui
- Zheng, Qinxiang
- Chen, Wei
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-10-03
- Volume
- 11
- Issue
- 43
- Pages
- 39603-39612
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W2978598381
- Cited by
- 88
- References
- 48
- Citations by year
- 2026: 5 · 2025: 20 · 2024: 14 · 2023: 17 · 2022: 12 · 2021: 15 · 2020: 5
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology of the People's Republic of China (2016YFC1101201)
- National Natural Science Foundation of China (31600807, 81500700)
- Natural Science Foundation of Zhejiang Province (LY19H120002, LY16H120008)
- State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Optometry and Ophthalmology, Wenzhou Medical University (K171204)
- 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
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- topical ocular drug delivery, polymeric micelles, tacrolimus, dry eye, corneal permeability, drug retention, ocular surface inflammation
- MeSH terms
- Administration, Topical, Animals, Cornea, Micelles, Ophthalmic Solutions, Peptides, Permeability, Rabbits, Dry Eye Syndromes, Tacrolimus
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