Development of dextrin-amphotericin B formulations for the treatment of Leishmaniasis
| Autor: | Moacir Fernandes Queiroz, Karoline Rachel Teodosio Melo, Tânia Cruz, H.A. Rocha, Ana M. Tomás, S. Leal, R. Silva-Carvalho, Miguel Gama, Joaquim Fidalgo, Pier Parpot |
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| Přispěvatelé: | Universidade do Minho |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
animal diseases
Drug Compounding Antiprotozoal Agents 02 engineering and technology Biochemistry Hemolysis 03 medical and health sciences Structural Biology Amphotericin B Dextrin parasitic diseases Dextrins medicine Cytotoxicity Molecular Biology IC50 Leishmaniasis 030304 developmental biology chemistry.chemical_classification Water dispersible Leishmania 0303 health sciences Chromatography Science & Technology urogenital system technology industry and agriculture General Medicine 021001 nanoscience & nanotechnology medicine.disease bacterial infections and mycoses 3. Good health chemistry Toxicity Delivery system 0210 nano-technology medicine.drug |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| Popis: | The most effective medicines available for the treatment of leishmaniasis, a life-threatening disease, exhibit serious toxicological issues. To achieve better therapeutic efficiency while decreasing toxicity associated with amphotericin B (AmB), water-soluble dextrin-AmB (Dex-AmB) formulations were developed. Self-assembled nanocomplexes were formed by dissolving Dex and AmB in alkaline borate buffer, followed by dialysis and either freeze-drying (FD) or nano spray-drying (SD), yielding water dispersible particles with a diameter of 214nm and 347nm, respectively. The very simple production process allowed the formation of amorphous inclusion complexes containing 14% of AmB in the form of monomers and water-soluble aggregates. Nanocomplexes were effective against parasites in axenic culture (IC50 of 0.056 and 0.096M for L. amazonensis and 0.030 and 0.044M for L. infantum, respectively for Dex-AmB FD and Dex-AmB SD) and in decreasing the intramacrophagic infection with L. infantum (IC50 of 0.017 and 0.023M, respectively for Dex-AmB FD and Dex-AmB SD). Also, the formulations were able to significantly reduce the cytotoxicity of AmB. Overall, this study demonstrates the suitability of dextrin as an AmB carrier and the facile and inexpensive development of a delivery system for the treatment of leishmaniasis. This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/ BIO/04469/2019 and BioTecNorte operation (NORTE-01-0145-FEDER000004 - Underpinning Biotechnology to foster the north of Portugal bioeconomy and NORTE-01-0145-FEDER-000012 - Structured program on bioengineered therapies for Infectious diseases and tissue regeneration) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Ricardo Silva-Carvalho gratefully acknowledge FCT for the granted scholarship (SFRH/BD/118880/2016). Karoline Rachel Melo and Moacir Fernandes Queiroz gratefully acknowledge Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brasil for the granted scholarship. info:eu-repo/semantics/publishedVersion |
| Databáze: | OpenAIRE |
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