Abstract
This study aimed to improve the water solubility and cutaneous permeability of Amphotericin B (AmB) for the topical treatment of Leishmania major-induced cutaneous leishmaniasis (CL) using two topical liposome- and polyethylene glycol (PEG)ylated liposome-gel formulations. The topical gel formulations of AmB were developed by its encapsulation into liposome (Lip-AmB) and (PEG)ylated liposome (PEG-Lip-AmB) using the reverse-phase evaporation method. The nanoformulations were characterized using dynamic light scattering and spectrophotometry. Their biological effects were evaluated in vitro and in vivo using Wright-Giemsa staining, limiting dilution assay, and pathological studies. Lip-AmB and PEG-Lip-AmB with the size of 257 ± 12.5 nm and 237 ± 12 nm, respectively, were synthesized. PEG-Lip-AmB compared to Lip-AmB, was more potent to decrease the drug toxicity and increase the drug’s therapeutic effects. The results of in vivo studies were in agreement with the results of in vitro studies, in which PEG-Lip-AmB-loaded gel (PEG-Lip-AmB-Gel), compared to Lip-AmB-loaded gel, could decrease the lesion size and parasite burden by 1.7- and 1.6-fold, respectively. These results suggest PEG-Lip-AmB-Gel can be used as a promising carrier to improve the properties of AmB for topical application against CL.
Graphical Abstract
Highlights
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PEGylated liposome significantly decreased the toxicity of Amphotericin B in vitro
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PEGylated liposome significantly increased the killing effects of Amphotericin B against leishmania major in vitro
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Loading of Amphotericin B into PEGylated liposome caused a significant reduction in lesion size and parasite burden in vivo
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Loading of Amphotericin B into PEGylated liposome could significantly reduce the renal toxicity of the drug in vivo
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Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
This work was supported by the School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran, and we would like to show our gratitude to the colleagues for their support.
Author contributions
Conceptualization: HES and SEA, methodology: RB, software: SA, validation: RB and MBG, formal analysis: SA, investigation: RB, resources: SA, data curation: SEA, writing—original draft preparation: RB and HES, writing—review and editing: SA, MBG and SEA, visualization: SEA and MBG, supervision: SEA and HES. All authors have read and agreed to the published version of the manuscript.
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Boshrouyeh, R., Amari, S., Boshrouyeh Ghandashtani, M. et al. A topical gel nanoformulation of amphotericin B (AmB) for the treatment of cutaneous leishmaniasis (CL). J Sol-Gel Sci Technol 105, 768–780 (2023). https://doi.org/10.1007/s10971-023-06041-w
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DOI: https://doi.org/10.1007/s10971-023-06041-w