Stability, safety, and transcorneal mechanistic studies of ophthalmic lyophilized cyclosporine-loaded polymeric micelles
Open accessAbstract
INTRODUCTION: Cyclosporine-A (CsA) is generally used as an immunosuppressant and is also prescribed for some ophthalmic applications such as vernal keratoconjunctivitis and dry eye. However, it is limited clinically due to its low aqueous solubility and ocular bioavailability. METHODS: In this work, lyophilized methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) polymer micelles were prepared for ophthalmic formulations as a promising nanocarrier for hydrophobic drugs like CsA. A mPEG-PLA diblock polymer was synthesized by ring opening polymerization and CsA was loaded into mPEG-PLA micelles by a simple film dispersion method. A uniform design of experiments was utilized to optimize the final formulation. The obtained formulation was characterized for diameter (57.0±3.2 nm), entrapment efficiency % (98.51±1.4), and in vitro release. Moreover, incorporating the stabilizer mPEG2000 could increase the in vitro stability of the lyophilized CsA-loaded mPEG-PLA micelles. RESULTS: Results showed a sustained release of CsA from the micelles. Drug concentration and time-dependent cytotoxicity of human corneal epithelial-2 cells was observed. Additionally, the transcorneal mechanism of mPEG-PLA micelles was studied and the results showed that the mPEG-PLA micelles mainly absorbed by a paracellular pathway via corneal epithelial cells. CONCLUSION: Taken together, the results proved that this mPEG-PLA diblock polymer can be potentially used as a nanoscopic carrier to deliver hydrophobic drugs in a controlled manner to the ocular region and, thus, deserves further attention.
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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 [123]
The Results and discussion section reports increased CsA retention in rabbit tears for a selected mPEG-PLA micelle formulation and sustained release in vitro. It does not report a 4.5-fold retention increase versus 0.05% CsA emulsion or demonstrate prolonged therapeutic effects against dry eye disease. The emulsion is described in the Introduction, not used as the reported retention comparator. (LLM, conf=0.88)
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 [123]
The Results and discussion section, under “In vitro release study,” reports sustained CsA release from mPEG-PLA micelles. The “Physical stability of CsA micelle lyophilization” section reports stability of the lyophilized formulation under the tested conditions for 10 days, not at least 3 months. The three-month stability claim is therefore unsupported by our copy. (LLM, conf=0.90)
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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].”
Influential
- Authors
- Shen, Y., Yu, Y., Chaurasiya, B., Li, X., Xu, Y., Webster, T., Tu, J., & Sun, R.
- Affiliations
- China Pharmaceutical University (CN)
- Jiangsu University (CN)
- Northeastern University (US)
- Corresponding author
- Tu, Jiasheng
- Venue
- International Journal of Nanomedicine
- Publisher
- Informa UK Limited
- Published
- 2018-12
- Volume
- Volume 13
- Pages
- 8281-8296
- ISSN
- 1176-9114 (ISSN-L)
- 1178-2013
- PMC
- PMC6287540
- OpenAlex
- W2903292093
- Cited by
- 35
- References
- 50
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 2 · 2020: 7 · 2019: 1
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Nanomedicine (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- National Natural Science Foundation of China (81501579, 2017ZX09101001, 81673364)
- Jiangsu University
- China Postdoctoral Science Foundation (2017M610309)
- Government of Jiangsu Province (KYCX17_0674)
- Natural Science Foundation of Jiangsu Province (BK20150702)
- Nanjing Medical University (2016NJMU105)
- Priority Academic Program Development of Jiangsu Higher Education Institutions (81673364, 2017ZX09101001-005-003, 2016NJMU105, BK20150702, KYCX17_0674)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
- Keywords
- cyclosporine, polymeric micelles, mPEG-PLA, ocular drug delivery, corneal epithelial cells, paracellular pathway, sustained drug release, hydrophobic drug delivery, nanocarriers, cytotoxicity
- MeSH terms
- Animals, Cell Line, Cornea, Drug Carriers, Fluorescence, Freeze Drying, Humans, Hydrogen-Ion Concentration, Immunosuppressive Agents, Irritants, Micelles, Ophthalmic Solutions, Particle Size, Polyesters, Polyethylene Glycols, Polymers, Rabbits, Solubility, Temperature, Cyclosporine, Cell Death, Polymerization, Drug Liberation, Proton Magnetic Resonance Spectroscopy
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