Ion-paired moxifloxacin nanocrystal formulation improves treatment and prevention of ocular infection

Matthew B Appell¹, Kiersten Malmberg², Ashwin Pasupathy², Aditya Josyula², Jairo Ortiz³, Peter J McDonnell⁴, Nakul Shekhawat⁴, Kunal S Parikh⁵, Laura M Ensign⁶

Affiliations

¹ The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
² The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
³ The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA.
⁴ Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.
⁵ The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Bioengineering Innovation & Design, Johns Hopkins University, Baltimore, MD 21218, USA.
⁶ The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA; Department of Gynecology and Obstetrics and Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: lensign@jhmi.edu.

PMID: 40096866
PMCID: PMC11994289 (available on 2026-05-10)
DOI: 10.1016/j.jconrel.2025.113634

Ion-paired moxifloxacin nanocrystal formulation improves treatment and prevention of ocular infection

Matthew B Appell et al. J Control Release. 2025.

. 2025 May 10:381:113634.

doi: 10.1016/j.jconrel.2025.113634. Epub 2025 Mar 15.

Authors

Matthew B Appell¹, Kiersten Malmberg², Ashwin Pasupathy², Aditya Josyula², Jairo Ortiz³, Peter J McDonnell⁴, Nakul Shekhawat⁴, Kunal S Parikh⁵, Laura M Ensign⁶

Affiliations

¹ The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
² The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
³ The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA.
⁴ Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.
⁵ The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Bioengineering Innovation & Design, Johns Hopkins University, Baltimore, MD 21218, USA.
⁶ The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA; Department of Gynecology and Obstetrics and Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: lensign@jhmi.edu.

PMID: 40096866
PMCID: PMC11994289 (available on 2026-05-10)
DOI: 10.1016/j.jconrel.2025.113634

Abstract

Ocular infections may arise spontaneously or following penetrating globe injury or operation, such as corneal transplant or cataract extraction. Treatment and prophylaxis of bacterial infections using antibiotic eye drops requires a strict dosing regimen to avoid irreversible vision loss. At present, moxifloxacin eye drops are prescribed for use multiple times per day, leading to patient non-adherence, the emergence of bacterial resistance, and infection progression. The desire to avoid sub-lethal antibiotic dosing and visual impairment through inconsistent eye drop application motivates the development of a sustained release injectable formulation. Herein, we report the development of an ion-paired, nanocrystalline moxifloxacin formulation that provided increased intraocular antibiotic accumulation with a single subconjunctival injection compared to 3× daily eye drops. The sustained release functionality further led to improved or non-inferior prevention and treatment of Staphylococcus aureus-induced ocular infection in both rats and rabbits compared to gold standard intracameral moxifloxacin and moxifloxacin eye drops. By achieving therapeutically relevant moxifloxacin accumulation, this nanocrystalline moxifloxacin formulation may be a promising alternative to conventional therapies to achieve improved post-surgical infection prevention and bacterial keratitis treatment outcomes.

Keywords: Intracameral moxifloxacin; Ocular infection; Staphylococcus aureus; Subconjunctival; Vigamox.

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Conflict of interest statement

Declaration of competing interest M.B.A. and L.M.E. are named as inventors on a provisional patent related to the presented research filed by Johns Hopkins University. The other authors declare no competing interests.

References

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Ion-paired moxifloxacin nanocrystal formulation improves treatment and prevention of ocular infection

Affiliations

Ion-paired moxifloxacin nanocrystal formulation improves treatment and prevention of ocular infection

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical