Development of dextrin-amphotericin B formulations for the treatment of Leishmaniasis

• Published in: International journal of biological macromolecules 2020-06, Vol.153, p.276-288
• Main Authors: Silva-Carvalho, R., Fidalgo, J., Melo, K.R., Queiroz, M.F., Leal, S., Rocha, H.A., Cruz, T., Parpot, P., Tomás, A.M., Gama, M.
• Format: Article
• Language: English
• Subjects: Amphotericin B; Amphotericin B - chemistry; Amphotericin B - pharmacology; Amphotericin B - therapeutic use; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - therapeutic use; Dextrin; Dextrins - chemistry; Drug Compounding; Hemolysis - drug effects; Leishmania - drug effects; Leishmania - physiology; Leishmaniasis; Leishmaniasis - drug therapy; Science & Technology
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.03.019

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 214 nm and 347 nm, 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 0.096 μM for L. amazonensis and 0.030 and 0.044 μM 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 0.023 μM, 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. [Display omitted] •Dextrin-Amphotericin B nanocomplexes were prepared by freeze- and spray-drying.•A very simple, feasible and inexpensive formulation process was developed.•Self-assembled nanocomplexes increased the water solubility of AmB.•The formulation significantly reduced the toxicity of AmB.•Dextrin-Amphotericin B nanocomplexes display promising leishmanicidal activity.