Protective and antifungal properties of Nanodisk-Amphotericin B over commercially available Amphotericin B.

OBJECTIVE

Amphotericin B (AMB), a potent antifungal agent, has been employed as topical and systemic therapy for sinonasal fungal infections. A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) for the treatment of fungal infections has been recently developed to provide greater protection from AMB toxicity than current, clinically approved lipid-based formulations. The objective of the current study was to evaluate the safety and potency of ND-AMB for sinonasal delivery using an model.

METHODS

Human sinonasal tissue was harvested during endoscopic sinus surgery and grown at air-liquid interface until well-differentiated. Cultures were exposed to ND-AMB vs AMB and changes in K permeability and resistance were measured and recorded via Ussing chamber assay. Ciliary beat frequency (CBF) was analyzed in parallel as well as cytotoxic assay. Potency was assessed using real-time PCR measurement of the 18S rRNA.

RESULTS

Ussing chamber studies revealed K currents that increased rapidly within 30 s of adding AMB (10 μg/mL) to the apical side, indicating apical membranes had become permeable to K ions. In contrast, negligible induction of K current was obtained following addition of ND-AMB [AMB = (107.7 ± 15.9) μA/cm AMB vs ND-AMB = (2.3 ± 0.7) μA/cm ND-AMB;  = 0.005]. ND-AMB also protected nasal epithelial cells from cytotoxicity of AMB ( < 0.05). There was no difference in ciliary beat frequency between the two groups ( = 0.96). The expression of 18S rRNA with exposure of lower dose of ND-AMB was significantly lower compared to that with AMB ( < 0.05).

CONCLUSIONS

Data from the present study suggests ND-AMB protects human nasal epithelia membranes from AMB toxicity by protecting against apical cell K permeability while maintaining uncompromised antifungal property compared to AMB. ND-AMB could provide a novel topical therapy for sinonasal fungal diseases.