Publicação
Development of a water-soluble Dextrin-Amphotericin B formulation for the treatment of Leishmaniasis
| Resumo: | Leishmaniasis, a life-threatening disease caused by Leishmania parasites, has been classified as one of the most neglected tropical diseases, even though there are currently around 12 million people infected, mainly in poor and less developed countries. Nowadays, there are no effective vaccines to prevent human leishmaniasis and thus, the disease control relies on chemotherapy. Amphotericin B (AmB) is the most recommended drug but presents some major drawbacks, such as low water solubility and high toxicity. To circumvent these issues, liposomal formulations or micellar dispersions have been developed. Despite being on the market, these products still present either major clinical limitations or a high-cost, hampering its use worldwide. Polysaccharide-based AmB delivery systems have emerged as an alternative treatment. Those formulations are developed through a polysaccharide backbone modification (oxidation) that allows a drug covalent conjugation. However, previous studies (unpublished data) done in our research group showed that chemical modifications are dispensable. In this work, dextrin is proposed as a suitable polysaccharide for the development of an AmB formulation. A Dextrin-AmB formulation was produced through a self-assembling process involving weaker forces, with an overall yield of 71.1%. The developed nanoformulation presented a spherical form when in aqueous solution, with a mean diameter of 244 nm (NTA) to 460 nm (DLS). An HPLC-MS method was developed and allowed to determine an AmB recovery efficiency (RE) and content of 134 % and 37.62 % (w/w), respectively. The nanoformulation did not present in vitro cytotoxicity to BMMf. Moreover, in vitro assays against Leishmania axenic promastigotes and intramacrophagic amastigotes showed a promising antileishmanial capacity, similar to the one displayed by free-AmB. |
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| Autores principais: | Fidalgo, João Miguel Pereira |
| Assunto: | Leishmaniasis Dextrin Amphotericin B Nanoparticles Leishmaniose Dextrino Anfotericina B Nanopartículas |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Leishmaniasis, a life-threatening disease caused by Leishmania parasites, has been classified as one of the most neglected tropical diseases, even though there are currently around 12 million people infected, mainly in poor and less developed countries. Nowadays, there are no effective vaccines to prevent human leishmaniasis and thus, the disease control relies on chemotherapy. Amphotericin B (AmB) is the most recommended drug but presents some major drawbacks, such as low water solubility and high toxicity. To circumvent these issues, liposomal formulations or micellar dispersions have been developed. Despite being on the market, these products still present either major clinical limitations or a high-cost, hampering its use worldwide. Polysaccharide-based AmB delivery systems have emerged as an alternative treatment. Those formulations are developed through a polysaccharide backbone modification (oxidation) that allows a drug covalent conjugation. However, previous studies (unpublished data) done in our research group showed that chemical modifications are dispensable. In this work, dextrin is proposed as a suitable polysaccharide for the development of an AmB formulation. A Dextrin-AmB formulation was produced through a self-assembling process involving weaker forces, with an overall yield of 71.1%. The developed nanoformulation presented a spherical form when in aqueous solution, with a mean diameter of 244 nm (NTA) to 460 nm (DLS). An HPLC-MS method was developed and allowed to determine an AmB recovery efficiency (RE) and content of 134 % and 37.62 % (w/w), respectively. The nanoformulation did not present in vitro cytotoxicity to BMMf. Moreover, in vitro assays against Leishmania axenic promastigotes and intramacrophagic amastigotes showed a promising antileishmanial capacity, similar to the one displayed by free-AmB. |
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