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Amphotericin B-loaded deformable lipid vesicles for topical treatment of cutaneous leishmaniasis skin lesions

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Abstract

Cutaneous leishmaniasis (CL), the most common clinical form of human leishmaniasis, is a non-fatal chronic and disabling disease characterized by erythema and nodular or ulcerative skin lesions that may cause permanent scars and disfigurement. Topical drug delivery represents a simple and efficacious approach to treat CL skin lesions. The association of drugs with nanocarrier systems enhances their permeation properties and increases the drug amount available in the dermis. Here, a deformable lipid vesicle (DLV) was optimized for the topical administration of Amphotericin B (AmB), with the aim of studying and understanding the advantages of this type of delivery system in the transport of a drug through the skin layers. AmB-DVL were characterized in terms of incorporation parameters, stability, and elasticity, and evaluated in vitro for their permeation properties, cytotoxicity, and anti-leishmanial activity. The AmB-DVL exhibited a translucent fluid gel-like aspect and a yellow color, a mean size of 132 nm (PdI ≤ 0.1), zeta potential values around zero (mV), and an AmB incorporation efficiency of 95%. Permeation and penetration assays suggest that AmB-DLV are suitable for topical administration since AmB was detected in the epidermal and dermal skin layers. AmB-DVL was able to reduce promastigote viability in a dose-dependent manner, as well as the number of intracellular amastigotes in THP-1 macrophages. Selectivity index (SI) value for AmB-DLV was considerably higher than that observed for free AmB. Results suggest that DLV may represent an attractive vehicle for dermal delivery of AmB and a new low-cost and safe therapeutic option in CL treatment.

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Funding

This work was partially funded by Fundação para a Ciência e a Tecnologia (FCT) through the program UID/DTP/04138/2019 and UIDB/04138/2020.

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Authors and Affiliations

  1. Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisboa, Portugal

    Manuela Carvalheiro, Catarina Faria-Silva, Joana Marto & Sandra Simões

  2. Faculty of Pharmacy, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisboa, Portugal

    Jennifer Vieira

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  1. Manuela Carvalheiro
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Contributions

Conceptualization: Manuela Carvalheiro; Methodology: Jennifer Vieira, Catarina Faria-Silva, Joana Marto, Manuela Carvalheiro, Sandra Simões; Software: Catarina Faria-Silva; Analysis: Manuela Carvalheiro, Sandra Simões; Original draft preparation: Jennifer Vieira; Review and editing: Manuela Carvalheiro, Sandra Simões, Catarina Faria-Silva. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Sandra Simões.

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Carvalheiro, M., Vieira, J., Faria-Silva, C. et al. Amphotericin B-loaded deformable lipid vesicles for topical treatment of cutaneous leishmaniasis skin lesions. Drug Deliv. and Transl. Res. 11, 717–728 (2021). https://doi.org/10.1007/s13346-021-00910-z

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