Nanocrystalline Chloroxine Possesses Broad-Spectrum Antimicrobial Activities and Excellent Skin Tolerability in Mice

Abstract

Background: Antimicrobial submicrometer particles are being studied as promising interventions against a wide range of skin conditions, such as fungal or bacterial infections. Aims: To submicronize chloroxine, the crystalline compound 5,7-dichloro-8-hydroxyquinoline, by nanoprecipitation and characterize the resulting assemblies. Methods: The chloroxine particles were stabilized by a nonionic surfactant and were studied by a broth microdilution assay against 20 medically important bacteria and fungi. The intervention was studied using a murine model of skin irritation. Results & conclusion: Chloroxine nanoparticles with a diameter of 600–800 nm exhibit good tolerability in terms of skin irritation in vivo and good antimicrobial activity. Thus, the fabricated formulation shows great promise for interventions for both cutaneous infection control and prophylaxis.

Graphical abstract

Keywords::

• dermal infections
• dermal safety
• nanomedicine
• nanoparticle-based intervention
• submicronization

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2021-0323

Author contributions

J Trousil designed and formulated the chloroxine particles and all of the experimental testing. Particle physicochemical characterization was carried out by both J Trousil and T Nejedlý. T Urbánek helped with physicochemical characterization and reviewed the manuscript. Biological testing was carried out by both J Trousil and J Matějková. M Šlouf was responsible for the TEM analysis. Y-S Dai and J-Y Fang were responsible for the in vivo experiments. M Škorič helped with the histopathology result description. J Trousil and T Urbánek wrote the manuscript. M Hrubý proposed the concept of chloroxine submicronization/stabilization and reviewed the manuscript.

Financial & competing interests disclosure

J Trousil acknowledges financial support from the Czech Academy of Sciences (project no. MSM200502101). M Hrubý acknowledges financial support from the Czech Science Foundation (grant no. 21-01090S). The antimicrobial testing part at the Military Health Institute laboratories was supported by funding from the project of Ministry of Defense of the Czech Republic through long-term organization development plan no. 907930101413. The authors have no other 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 apart from those that have been disclosed.

Writing assistance from American Journal Experts was utilized in the production of this manuscript and was funded by the Czech Academy of Sciences (project no. MSM200502101).

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Additional information

Funding

J Trousil acknowledges financial support from the Czech Academy of Sciences (project no. MSM200502101). M Hrubý acknowledges financial support from the Czech Science Foundation (grant no. 21-01090S). The antimicrobial testing part at the Military Health Institute laboratories was supported by funding from the project of Ministry of Defense of the Czech Republic through long-term organization development plan no. 907930101413. The authors have no other 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 apart from those that have been disclosed.