Short imidazolium chains effectively clear fungal biofilm in keratitis treatment

Area of Science:

• Ophthalmology
• Infectious Diseases
• Polymer Chemistry

Background:

• Fungal keratitis is a significant global cause of vision loss.
• Existing treatments for fungal keratitis often lack efficacy and can be unstable or expensive.
• There is a critical need for novel, effective, and accessible antifungal agents.

Purpose of the Study:

• To develop and evaluate novel amphiphilic main-chain imidazolium polymer (PIM-45) and oligomer (IBN-1) materials for treating fungal keratitis.
• To assess the antifungal activity, safety (hemolysis), and in vivo efficacy of these polyimidazolium salts (PIMSs).
• To compare the properties of PIMSs with existing antifungal drugs like amphotericin B and fluconazole.

Main Methods:

• Synthesis of amphiphilic main-chain imidazolium polymer (PIM-45) and oligomer (IBN-1).
• Determination of minimal inhibition concentration (MIC) values against fungi and assessment of biofilm clearance.
• Evaluation of hemolytic activity to determine safety.
• In vivo studies using topical PIMS solutions to treat Candida albicans keratitis in animal models.

Main Results:

• PIM-45 and IBN-1 demonstrated potent inhibition of fungal growth with low MIC values.
• These PIMSs effectively cleared fungal biofilms and exhibited minimal hemolysis, indicating good safety.
• In vivo treatment showed PIMSs were as effective as amphotericin B for Candida albicans keratitis.
• The developed PIMSs are stable, inexpensive, and easy to prepare, with a long shelf life in PBS solutions.

Conclusions:

• Amphiphilic polyimidazolium salts (PIMSs), specifically PIM-45 and IBN-1, represent a new class of safe and effective agents against fungal keratitis.
• These novel materials offer significant advantages over current therapies, including cost-effectiveness, stability, and ease of preparation.
• PIMSs hold great promise for routine topical use in managing fungal eye infections.