Nanosystems Formed By Amphiphilic Antimony(v) Complexes Incorporating Amphotericin B For The Treatment Leishmaniasis | 33979
Journal of Biotechnology & Biomaterials
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This work aimed to developan oral formulation of amphotericin B (AmB) for treatment of leishmaniasis. AmB is an antifungal
and antibacterial macrolide polyenederived from Streptomyces nodosus strain, that belongs to the group of second
generation anti-leishmanial drugs and is extensively used in case of failures in the treatment with antimonial compounds. AmB
was incorporated into nanosystems formed by amphiphilic antimony(V) complexes with ligands of alkylmethylglucamide
series (L8 and L10, with 8 and 10 carbon chain, respectively). Incorporation rate of 0.2% AmB into SbL8 and SbL10 dispersions
was determined using an HPLC-based technique and was found to be 84±1% and 74±1%, respectively. The characterizarion of
SbL10-AmB and SbL8-AmB by circular dichroism and UV-visible spectroscopies showed that AmB is present predominantly
under the monomeric form in both SbL8 and Sb10 nanosystems, which is the least toxic form to the host and potentially most
bioavailable. The potential for the oral treatment of visceral (VL) and cutaneous leishmaniasis (CL) was evaluated in murine
models in comparison to the standard drug Anforicin B® or Glucantime® administered intraperitoneally or orally. In Balb/c
mice infected with Leishmania amazonensis, the SbL10-AmB mixed formulation (170 mgSb/kg and 14 mg AmB/kg, each 2
days by oral route) resulted in a significant decrease of the lesion size, when compared to orally administetred Glucantime® and
SbL10 (170 mg Sb/kg, each 2 days), Anforicin B® (>1mg/kg/each 5th day, by intraperitoneal route) and control saline group. In
Balb/c mice infected with Leishmania infantum, both the SbL10-AmB and SbL8-AmB mixed formulations given orally (170
mg Sb/kg and 14 mg AmB/kg per day) reduced significantly the parasite load in the liver compared to the untreated control, to
a similar level as AmB given intraperitoneally (0.9 mg/kg/day). This study established for the first time the potential of mixed
SbL10-AmB and SbL8-AmB formulations for the oral treatment of both cutaneous and visceral leishmaniasis, indicating their
potential for further development and applications.
Arshad Islam has completed his PhD from Universidade Federal de Minas Gerais, Brazil and currently working as Post-doctoral researcher at Laboratory of Biophysics and Nanostructured Systems, Department of Physiology and Biophysics, Institute of Biological Sceinces, Universidade Federal de Minas Gerais. He has published 4 papers in reputed journals.