Ultradeformable lipid vesicles localize amphotericin B in the dermis for the treatment of infectious skin diseases
Fernández-Garciá, Raquel and Statts, Larry and De Jesus, Jéssica A. and Dea-Ayuela, Maria Auxiliadora and Bautista, Liliana and Simaõ, Rúben and Bolás-Fernández, Francisco and Ballesteros, Maria Paloma and Laurenti, Marcia Dalastra and Passero, Luiz F.D. and Lalatsa, Aikaterini and Serrano, Dolores R. (2020) Ultradeformable lipid vesicles localize amphotericin B in the dermis for the treatment of infectious skin diseases. ACS Infectious Diseases, 6 (10). pp. 2647-2660. (https://doi.org/10.1021/acsinfecdis.0c00293)
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Abstract
Cutaneous fungal and parasitic diseases remain challenging to treat, as available therapies are unable to permeate the skin barrier. Thus, treatment options rely on systemic therapy, which fail to produce high local drug concentrations but can lead to significant systemic toxicity. Amphotericin B (AmB) is highly efficacious in the treatment of both fungal and parasitic diseases such as cutaneous leishmaniasis but is reserved for parenteral administration in patients with severe pathophysiology. Here, we have designed and optimized AmB-transfersomes [93.5% encapsulation efficiency, 150 nm size, and good colloidal stability (-35.02 mV)] that can remain physicochemically stable (>90% drug content) at room temperature and 4 °C over 6 months when lyophilized and stored under desiccated conditions. AmB-transfersomes possessed good permeability across mouse skin (4.91 ± 0.41 μg/cm2/h) and 10-fold higher permeability across synthetic Strat-M membranes. In vivo studies after a single topical application in mice showed permeability and accumulation within the dermis (>25 μg AmB/g skin 6 h postadministration), indicating the delivery of therapeutic amounts of AmB for mycoses and cutaneous leishmaniasis, while a single daily administration in Leishmania (Leishmania) amazonensis infected mice over 10 days, resulted in excellent efficacy (98% reduction in Leishmania parasites). Combining the application of AmB-transfersomes with metallic microneedles in vivo increased the levels in the SC and dermis but was unlikely to elicit transdermal levels. In conclusion, AmB-transfersomes are promising and stable topical nanomedicines that can be readily translated for parasitic and fungal infectious diseases.
ORCID iDs
Fernández-Garciá, Raquel, Statts, Larry, De Jesus, Jéssica A., Dea-Ayuela, Maria Auxiliadora, Bautista, Liliana, Simaõ, Rúben, Bolás-Fernández, Francisco, Ballesteros, Maria Paloma, Laurenti, Marcia Dalastra, Passero, Luiz F.D., Lalatsa, Aikaterini ORCID: https://orcid.org/0000-0003-4791-7468 and Serrano, Dolores R.;-
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Item type: Article ID code: 81138 Dates: DateEvent9 October 2020Published18 August 2020Published Online8 May 2020AcceptedSubjects: Medicine > Pharmacy and materia medica Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 17 Jun 2022 05:36 Last modified: 03 Oct 2024 03:30 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/81138