2. Academic Validation
  3. In-vitro and in-vivo antileishmanial activity of inexpensive Amphotericin B formulations: Heated Amphotericin B and Amphotericin B-loaded microemulsion

In-vitro and in-vivo antileishmanial activity of inexpensive Amphotericin B formulations: Heated Amphotericin B and Amphotericin B-loaded microemulsion

  • Exp Parasitol. 2018 Sep;192:85-92. doi: 10.1016/j.exppara.2018.07.017.
Andreza Rochelle do Vale Morais 1,  André Leandro Silva 2,  Sandrine Cojean 3,  Kaluvu Balaraman 4,  Christian Bories 3,  Sébastien Pomel 3,  Gillian Barratt 5,  Eryvaldo Sócrates Tabosa do Egito 6,  Philippe M Loiseau 7
Affiliations

Affiliations

  • 1 Universidade Federal do Rio Grande do Norte (UFRN), Programa de Pós-graduação em Nanotecnologia Farmacêutica, Rua Gustavo Cordeiro de Farias, SN. Petrópolis, CEP: 59012-570 Natal, RN, Brazil; Université Paris-Sud, Institut Galien Paris-Sud, UMR-CNRS 8612, 5, Rue Jean-Baptiste Clément, 92296 Châtenay-Malabry cedex, France.
  • 2 UFRN, Programa de Pós-graduação em Biotecnologia (RENORBIO), Av. Senador Salgado Filho, 3000. Campus Universitário, CEP: 59078-970 Natal, RN, Brazil; Université Paris-Sud, Institut Galien Paris-Sud, UMR-CNRS 8612, 5, Rue Jean-Baptiste Clément, 92296 Châtenay-Malabry cedex, France; Centro das Ciências Biológicas e da Saúde, Universidade Federal do Oeste da Bahia (UFOB), R. Prof. José Seabra de Lemos, 316, CEP: 47.808-021 Barreiras, BA, Brazil.
  • 3 Université Paris-Sud, Faculté de Pharmacie, UMR 8076 CNRS BioCIS, Châtenay-Malabry, France.
  • 4 Université Paris-Sud, Faculté de Pharmacie, UMR 8076 CNRS BioCIS, Châtenay-Malabry, France; Chemical Biology Lab, Department of Biotechnology, IITM, Technology Madras, Chennai, India.
  • 5 Université Paris-Sud, Institut Galien Paris-Sud, UMR-CNRS 8612, 5, Rue Jean-Baptiste Clément, 92296 Châtenay-Malabry cedex, France.
  • 6 Universidade Federal do Rio Grande do Norte (UFRN), Programa de Pós-graduação em Nanotecnologia Farmacêutica, Rua Gustavo Cordeiro de Farias, SN. Petrópolis, CEP: 59012-570 Natal, RN, Brazil; UFRN, Programa de Pós-graduação em Biotecnologia (RENORBIO), Av. Senador Salgado Filho, 3000. Campus Universitário, CEP: 59078-970 Natal, RN, Brazil.
  • 7 Université Paris-Sud, Faculté de Pharmacie, UMR 8076 CNRS BioCIS, Châtenay-Malabry, France. Electronic address: [email protected].
PMID: 30075233 DOI: 10.1016/j.exppara.2018.07.017
Abstract

Amphotericin B (AmB) is effective against visceral leishmaniasis (VL), but the renal toxicity of the conventional form, mixed micelles with deoxycholate (M-AmB), is often dose-limiting, while the less toxic lipid-based formulations such as AmBisome® are very expensive. Two different strategies to improve the therapeutic index of AmB with inexpensive ingredients were evaluated on this work: (i) the heat treatment of the commercial formulation (H-AmB) and (ii) the preparation of an AmB-loaded microemulsion (ME-AmB). M-AmB was heated to 70 °C for 20 min. The resulting product was characterized by UV spectrophotometry and circular dichroism, showing super-aggregates formation. ME-AmB was prepared from phosphate buffer pH 7.4, Tween 80®, Lipoid S100® and Mygliol 812® with AmB at 5 mg/mL. The droplet size, measured by dynamic LIGHT scattering, was about 40 nm and transmission electron microscopy confirmed a spherical shape. Rheological analysis showed low viscosity and Newtonian behavior. All the formulations were active in vitro and in vivo against Leishmania donovani (LV9). A selectivity index (CC50 on RAW/IC50 on LV9) higher than 10 was observed for ME-AmB, H-AmB and AmBisome®. Furthermore, no important in vivo toxicity was observed for all the samples. The in-vivo efficacy of the formulations after IV administration was evaluated in Balb/C mice infected with LV9 (three doses of 1 mg/kg AmB) and no significant difference was observed between H-AmB, M-AmB, ME-AmB and AmBisome®. In conclusion, these two inexpensive alternative formulations for AmB showing good efficacy and selectivity for Leishmania donovani merit further investigation.

Keywords

Amphotericin B; Microemulsion; Superaggregates; Visceral leishmaniasis.

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