Magnetic hyperthermia adjunctive therapy for fungi: in vitro studies against Candida albicans.

The poor penetration of anti-fungal agents into the cornea through the intact epithelium layer makes it difficult to treat acute fungal corneal infections. Herein, we developed Amphotret (amphotericin B) antifungal drug contained polycaprolactone-Fe3O4 (PCL-FO) magnetic nanofibers (MNFs) using the electrospinning technique. These MNFs generate heat in the presence of AC magnetic field (AMF) and release drug upon heating. MNFs were compatible with human mesenchymal stem cells (hMSCs) and HeLa cells, which exhibited unaltered proliferation, ruling out any toxicity from the systems. Hyperthermia induced via MNFs from 42 °C to 50 °C compromised the viability of Candida albicans cells. Further, the efficacy of the systems was increased in the presence of both heat and drug simultaneously in vitro, leading to near 100% loss in viability of C. albicans cells at 50 °C with simultaneous drug release from MNFs. Thus, we propose magnetic hyperthermia as adjunctive therapy for fungal keratitis.

Chitosan Derivatives Active against Multidrug-Resistant Bacteria and Pathogenic Fungi: In Vivo Evaluation as Topical Antimicrobials.

The continuous rise of antimicrobial resistance and the dearth of new antibiotics in the clinical pipeline raise an urgent call for the development of potent antimicrobial agents. Cationic chitosan derivatives, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chlorides (HTCC), have been widely studied as potent antibacterial agents. However, their systemic structure-activity relationship, activity toward drug-resistant bacteria and fungi, and mode of action are very rare. Moreover, toxicity and efficacy of these polymers under in vivo conditions are yet to be established. Herein, we investigated antibacterial and antifungal efficacies of the HTCC polymers against multidrug resistant bacteria including clinical isolates and pathogenic fungi, studied their mechanism of action, and evaluated cytotoxic and antimicrobial activities in vitro and in vivo. The polymers were found to be active against both bacteria and fungi (MIC = 125-250 µg/mL) and displayed rapid microbicidal kinetics, killing pathogens within 60-120 min. Moreover, the polymers were shown to target both bacterial and fungal cell membrane leading to membrane disruption and found to be effective in hindering bacterial resistance development. Importantly, very low toxicity toward human erythrocytes (HC50 = >10000 µg/mL) and embryo kidney cells were observed for the cationic polymers in vitro. Further, no inflammation toward skin tissue was observed in vivo for the most active polymer even at 200 mg/kg when applied on the mice skin. In a murine model of superficial skin infection, the polymer showed significant reduction of methicillin-resistant Staphylococcus aureus (MRSA) burden (3.2 log MRSA reduction at 100 mg/kg) with no to minimal inflammation. Taken together, these selectively active polymers show promise to be used as potent antimicrobial agents in topical and other infections.