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 g...
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KeAi Communications Co., Ltd.
2017
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oai:doaj.org-article:c49247a315f544d5a5027b325173e8652021-12-02T12:54:49ZProtective and antifungal properties of Nanodisk-Amphotericin B over commercially available Amphotericin B2095-881110.1016/j.wjorl.2017.01.002https://doaj.org/article/c49247a315f544d5a5027b325173e8652017-03-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2095881117300082https://doaj.org/toc/2095-8811Objective: 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 in vitro model. Methods: Human sinonasal tissue was harvested during endoscopic sinus surgery and grown at airâliquid 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 Aspergillus fumigatus 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/cm2 AMB vs ND-AMB = (2.3 ± 0.7) μA/cm2 ND-AMB; P = 0.005]. ND-AMB also protected nasal epithelial cells from cytotoxicity of AMB (P < 0.05). There was no difference in ciliary beat frequency between the two groups (P = 0.96). The expression of A. fumigatus 18S rRNA with exposure of lower dose of ND-AMB was significantly lower compared to that with AMB (P < 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. Keywords: Chronic rhinosinusitis, Amphotericin, Drug delivery, Transepithelial ion transport, Sinusitis, Sinus epithelium, Mucociliary clearance, Ciliary beat frequencyDo-Yeon ChoKyle J. HoffmanGobind S. GillDong-Jin LimDaniel SkinnerCalvin MackeySteven M. RoweBradford A. WoodworthKeAi Communications Co., Ltd.articleOtorhinolaryngologyRF1-547SurgeryRD1-811ENWorld Journal of Otorhinolaryngology-Head and Neck Surgery, Vol 3, Iss 1, Pp 2-8 (2017) |
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Otorhinolaryngology RF1-547 Surgery RD1-811 |
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Otorhinolaryngology RF1-547 Surgery RD1-811 Do-Yeon Cho Kyle J. Hoffman Gobind S. Gill Dong-Jin Lim Daniel Skinner Calvin Mackey Steven M. Rowe Bradford A. Woodworth Protective and antifungal properties of Nanodisk-Amphotericin B over commercially available Amphotericin B |
| description |
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 in vitro model. Methods: Human sinonasal tissue was harvested during endoscopic sinus surgery and grown at airâliquid 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 Aspergillus fumigatus 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/cm2 AMB vs ND-AMB = (2.3 ± 0.7) μA/cm2 ND-AMB; P = 0.005]. ND-AMB also protected nasal epithelial cells from cytotoxicity of AMB (P < 0.05). There was no difference in ciliary beat frequency between the two groups (P = 0.96). The expression of A. fumigatus 18S rRNA with exposure of lower dose of ND-AMB was significantly lower compared to that with AMB (P < 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. Keywords: Chronic rhinosinusitis, Amphotericin, Drug delivery, Transepithelial ion transport, Sinusitis, Sinus epithelium, Mucociliary clearance, Ciliary beat frequency |
| format |
article |
| author |
Do-Yeon Cho Kyle J. Hoffman Gobind S. Gill Dong-Jin Lim Daniel Skinner Calvin Mackey Steven M. Rowe Bradford A. Woodworth |
| author_facet |
Do-Yeon Cho Kyle J. Hoffman Gobind S. Gill Dong-Jin Lim Daniel Skinner Calvin Mackey Steven M. Rowe Bradford A. Woodworth |
| author_sort |
Do-Yeon Cho |
| title |
Protective and antifungal properties of Nanodisk-Amphotericin B over commercially available Amphotericin B |
| title_short |
Protective and antifungal properties of Nanodisk-Amphotericin B over commercially available Amphotericin B |
| title_full |
Protective and antifungal properties of Nanodisk-Amphotericin B over commercially available Amphotericin B |
| title_fullStr |
Protective and antifungal properties of Nanodisk-Amphotericin B over commercially available Amphotericin B |
| title_full_unstemmed |
Protective and antifungal properties of Nanodisk-Amphotericin B over commercially available Amphotericin B |
| title_sort |
protective and antifungal properties of nanodisk-amphotericin b over commercially available amphotericin b |
| publisher |
KeAi Communications Co., Ltd. |
| publishDate |
2017 |
| url |
https://doaj.org/article/c49247a315f544d5a5027b325173e865 |
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