Hyaluronic acid-amphotericin B nanocomplexes: a promising anti-leishmanial drug delivery system

The development of an effective amphotericin B (AmB) formulation to replace actual treatments available for leishmaniasis, which present serious drawbacks, is a challenge. Here we report the development of hyaluronic acid-amphotericin B self-assembled nanocomplexes (HA-AmB), processed by freeze-dryi...

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Veröffentlicht in:Biomaterials science 2022-04, Vol.1 (8), p.1952-1967
Hauptverfasser: Silva-Carvalho, R, Leão, T, Bourbon, A. I, Gonçalves, C, Pastrana, L. M, Parpot, P, Amorim, I, Tomás, A. M, Gama, F. M
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Sprache:eng
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Zusammenfassung:The development of an effective amphotericin B (AmB) formulation to replace actual treatments available for leishmaniasis, which present serious drawbacks, is a challenge. Here we report the development of hyaluronic acid-amphotericin B self-assembled nanocomplexes (HA-AmB), processed by freeze-drying (FD) or nano spray-drying (SD), using a simple process that favors the non-covalent drug-polysaccharide association in an amorphous state. These water-soluble formulations, which presented a nanometric size (300-600 nm), high colloidal stability (zeta potential around −39 mV) and an AmB loading (15-18%) in aggregated and super aggregated states, demonstrated less in vitro cytotoxic and hemolytic effects compared to the free-drug. A significant decrease in the number of intramacrophagic L. infantum amastigotes upon treatment (IC 50 of 0.026 and 0.030 μM for HA-AmB FD and HA-AmB SD, respectively) was also observed, and the best selectivity index (SI) was observed for the HA-AmB SD nanocomplex (SI of 651). Intravenous administration of the HA-AmB SD nanocomplex for 3 alternate days showed an effective parasite reduction in the spleen and liver of C57BL/6 mice without signs of toxicity commonly observed upon free-AmB treatment. Although lower than that achieved with AmBisome® in the liver, the observed parasite reduction for the nanocomplex was of a similar order of magnitude. The efficacy, stability, safety and low cost of the HA-AmB SD nanocomplex highlight its potential as an alternative treatment for leishmaniasis. Hyaluronic acid-Amphotericin B self-assembled nanocomplexes obtained by a simple drug-polysaccharide non-covalent association in an amorphous state exhibit potent anti-leishmanial activity and can overcome drug toxicity.
ISSN:2047-4830
2047-4849
DOI:10.1039/d1bm01769a