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.

KEYWORDS:

• Micelle
• natamycin
• eye drop
• sustained release
• fungal keratitis

Author contributions

Yiyuan Guo, Fatemeh Karimi, and Qiang Fu were involved in conception, design, performing experiments, analysis of data, and writing the manuscript. Hong Zhang and Greg. G. Qiao were involved in conception and guidance to perform experiments.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have received an honorarium from Expert Opinion on Drug Delivery for their review work, but have no other relevant financial relationships to disclose.

Supplemental material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by The National Natural Science Foundation of China [81970776; 81671844] and The Scientific Research Transformation of Foundation of Heilongjiang Academy of Medical Sciences (CR201809). All authors acknowledge the funding provided by the Australian Research Council under the ARC Linkage Grant [LP150100315] and Heilongjiang Harbin Medical Pharmaceutical co. LTD.