Improving the topical ocular pharmacokinetics of lyophilized cyclosporine A-loaded micelles: formulation, in vitro and in vivo studies
Open accessAbstract
Dry eye syndrome (DES) is one of the most common disorders of the eye for which combined treatment includes modification of the ocular environment and pathogenic therapies. Cyclosporine A (CsA), a immunosuppressive agent, has been demonstrated to be effective for the treatment of DES but is limited clinically by its low ocular bioavailability due to poor water solubility. In this paper, methoxy poly (ethylene glycol)-poly (lactide) polymer (mPEG-PLA) micelles were investigated as alternative vehicles for the solubilization and delivery of CsA to the eye. The in vitro stability indicated that CsA-loaded micellar lyophilized powder was stable for at least 3 months and the release profile showed a sustained release manner of CsA from micelles physically. In vivo ocular distribution studies demonstrated that the micellar formulations exhibited a 4.5-fold increase in retention effect at eyes compared with 0.05% CsA emulsion. In addition, the in vivo pharmacokinetics profile showed that the CsA-loaded micelles could enhance the retention time, achieving longer effect toward the DES. These studies proposed an effective micelle formulation as a novel ocular drug delivery system to improve solubility and bioavailability of ophthalmic CsA-controlled delivery.
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CsA-loaded mPEG-PLA formulations achieved a 4.5-fold increase in retention at eyes compared with 0.05% CsA emulsion, prolonging therapeutic effects against DED.
“These formulations achieved a 4.5-fold increase in retention at eyes compared with 0.05 % CsA emulsion, thus prolongating therapeutic effects against DED [122,123].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [122]
The Ocular distribution study (page unavailable) reports a 4.5-fold higher *maximum corneal CsA concentration* with mPEG-PLA micelles and longer ocular-surface residence, rather than a 4.5-fold increase in overall eye retention. It suggests these findings could benefit dry-eye treatment, but does not demonstrate prolonged therapeutic effects. The Introduction identifies a 0.05% commercial emulsion, while the Results passage describes the study comparator as 5%. (LLM, conf=0.85)
Experimental — accuracy not yet measuredCsA-loaded mPEG-PLA micelles remained stable for at least 3 months while realizing sustained release of CsA.
“The in vitro stability assessments indicated that CsA-loaded mPEG-PLA remained stable for at least 3 months while realizing the sustained release of CsA from micelles.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [122]
The Conclusions report that lyophilized micelles containing 5% mPEG2000 were stable for 3 months at 4 °C and showed sustained, delayed CsA release. The claim omits those stability conditions; the Physical stability study reports that formulations without sufficient mPEG2000 became unstable. (LLM, conf=0.88)
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“These formulations achieved a 4.5-fold increase in retention at eyes compared with 0.05 % CsA emulsion, thus prolongating therapeutic effects against DED [122,123].”
InfluentialDong, X., Cong, K., Lu, Y., Yang, S., Sun, Y., Hao, J., Liu, Y., Zhang, Y., Liu, C., He, C., et al. (2026) · Small · doi:10.1002/smll.74981
- Authors
- Yu, Y., Chen, D., Li, Y., Yang, W., Tu, J., & Shen, Y.
- Affiliations
- China Pharmaceutical University (CN)
- Yantai University (CN)
- Corresponding author
- Tu, Jiasheng
- Shen, Yan
- Venue
- Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2018-01-01
- Volume
- 25
- Issue
- 1
- Pages
- 888-899
- ISSN
- 1071-7544 (ISSN-L)
- 1521-0464
- PMC
- PMC6058700
- OpenAlex
- W2797901882
- Cited by
- 85
- References
- 51
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 11 · 2023: 18 · 2022: 13 · 2021: 2 · 2020: 14 · 2019: 13 · 2018: 2
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drug Delivery (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministry of Science and Technology of China (2017ZX09101001-005-003)
- National Natural Science Foundation of China (81501579, 81673364)
- Natural Science Foundation of Jiangsu Province (NO.BK20150702)
- Science and Technology Development Fund
- Nanjing Medical University (2016NJMU105)
- Jiangsu Province (KYCX17_0674)
- 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 › Drug Solubulity and Delivery Systems
- Keywords
- cyclosporine, dry eye, ocular drug delivery, micelles, mPEG-PLA, lyophilized powder, ocular bioavailability, sustained drug release, ocular retention, ocular pharmacokinetics, solubility enhancement, ophthalmic preparations
- MeSH terms
- Animals, Biological Availability, Cell Line, Delayed-Action Preparations, Drug Carriers, Drug Compounding, Drug Stability, Eye, Freeze Drying, Humans, Immunosuppressive Agents, Micelles, Polyesters, Polyethylene Glycols, Powders, Rabbits, Technology, Pharmaceutical, Tissue Distribution, Dry Eye Syndromes, Cyclosporine, Administration, Ophthalmic, Drug Liberation
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