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    Reduced administration frequency for the treatment of fungal keratitis: a sustained natamycin release from a micellar solution.

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    Author
    Guo, Y; Karimi, F; Fu, Q; G Qiao, G; Zhang, H
    Date
    2020-02-03
    Source Title
    Expert Opinion on Drug Delivery
    Publisher
    Taylor & Francis Ltd
    University of Melbourne Author/s
    Karimi, Fatemeh; GUO, YIYUAN; Fu, Qiang; Qiao, Greg
    Affiliation
    Chemical and Biomolecular Engineering
    Metadata
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    Document Type
    Journal Article
    Citations
    Guo, Y., Karimi, F., Fu, Q., G Qiao, G. & Zhang, H. (2020). Reduced administration frequency for the treatment of fungal keratitis: a sustained natamycin release from a micellar solution.. Expert Opin Drug Deliv, 17 (3), pp.407-421. https://doi.org/10.1080/17425247.2020.1719995.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/258691
    DOI
    10.1080/17425247.2020.1719995
    ARC Grant code
    ARC/LP150100315
    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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