Reduced administration frequency for the treatment of fungal keratitis: a sustained natamycin release from a micellar solution
Abstract
Background Natamycin is the only topical ophthalmic antifungal drug approved by the Food and Drug Administration (FDA) of the United States, but has unsatisfactory factors such as high dosing frequency.Methods We report the synthesis and preparation of self-assembled poly(ethylene glycol)-block-poly(glycidyl methacrylate) (PEG-b-PGMA) micelles. These nanoparticles exhibit sustained delivery of a hydrophobic natamycin by topical administration on eye due to the hydrolysable properties of PGMA segments of micelle. Hydrolysis of glycidyl groups within a physiologically relevant environment provides an additional driving force for drug release by generation of hydrophilic hydroxyl groups to ‘push’ the encapsulated hydrophobic drug away from the resultant hydrophilic domains and into surrounding environment.Results In vitro and in vivo results revealed that the self-assembled micelles and the encapsulated natamycin were not cytotoxic and the released drug have strong antifungal ability to Candida albicans. Importantly, sustained natamycin release from micelles leads to the reduced administration frequency of natamycin from 8 times per day to 3 times per day in rabbits suffering from fungal keratitis (FK).Conclusion This study demonstrates a facile method that can greatly reduce dosing frequency of natamycin administration and thus improve long-term patient compliance.
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The incorporation of PGMA into PEG-PGMA micelles endows them with controlled release since PGMA can be hydrolyzed to yield hydrophilic hydroxyl groups at neutral pH.
“The incorporation of PGMA into PEG–PGMA micelles endows them with the characteristics of controlled release since PGMA can be hydrolyzed to yield hydrophilic hydroxyl groups at neutral pH [209].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [209]
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“The incorporation of PGMA into PEG – PGMA micelles endows them with the characteristics of controlled release since PGMA can be hydrolyzed to yield hydrophilic hydroxyl groups at neutral pH [209].”
- Authors
- Guo, Y., Karimi, F., Fu, Q., G. Qiao, G., & Zhang, H.
- Affiliations
- Harbin Medical University (CN)
- The University of Melbourne (AU)
- University of Technology Sydney (AU)
- Department of Chemical Engineering, The University of Melbourne, Melbourne, Australia
- Corresponding author
- Zhang, Hong
- Venue
- Expert Opinion on Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2020-02-03
- Volume
- 17
- Issue
- 3
- Pages
- 407-421
- ISSN
- 1742-5247 (ISSN-L)
- 1744-7593
- OpenAlex
- W3004564308
- Cited by
- 36
- References
- 44
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 3
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Drug Delivery (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- OPUS - Open Publications of UTS Scholars (University of Technology Sydney) (submittedVersion)
- Funders
- National Natural Science Foundation of China (81970776; 81671844)
- Australian Research Council under the ARC Linkage (LP150100315)
- The Scientific Research Transformation of Foundation of Heilongjiang Academy of Medical Sciences (CR201809)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Ophthalmology › Ocular Infections and Treatments
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- natamycin, fungal keratitis, sustained drug release, micelles, nanoparticle self-assembly, Candida albicans, reduced dosing frequency, medication adherence
- MeSH terms
- Administration, Topical, Animals, Antifungal Agents, Humans, Keratitis, Micelles, Natamycin, Rabbits, Eye Infections, Fungal, Nanoparticles, Drug Liberation
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