Development of a water-soluble dextrin-amphotericin B conjugate for the treatment of Leishmaniasis

Leishmaniasis is a life-threatening disease with a worldwide distribution and a huge impact especially in immunocompromised patients. Nowadays, the use of amphotericin B, an antifungal agent, or other marketed strategies to overcome this disease exhibit major clinical limitations. Thus, other strategies have been pursued to achieve better clinical treatments and decrease toxicity. In this work, a promising conjugate based on dextrin and amphotericin B was developed. An HPLC-MS detection method was also developed in order to determine the amphotericin B concentration and the encapsulation efficiency. This water-soluble polymer-drug conjugate has shown promising effects against axenic cultures of Leishmania amazonensis parasite and infected macrophages, without being cytotoxic to the latter.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Ricardo Silva-Carvalho gratefully acknowledge the Portuguese Foundation for Science and Technology (FCT) for the granted scholarship (SFRH/BD/118880/2016).