Amphotericin B intercalated in layered clays as effective antifungal systems against eumycetoma causative agents

Abstract

Eumycetoma and other subcutaneous mycosis are severe chronic infections with a high incidence in tropical and subtropical regions, whose current treatment has a low curation rate. In the search for more effective and affordable therapies, hybrid materials based on amphotericin B (AmB), an antifungal drug with a broad spectrum of action, appear promising for localized treatment at the site of infection. In this context, the immobilization of AmB in suitable nanocarriers would be helpful to minimize its adverse side effects and ensure a controlled release over time. For this purpose, montmorillonite (MMT), showing cation exchange capacity, and layered double hydroxides (LDH), with anion exchange capacity, are explored as possible supports, taking advantage of the amphoteric character of AmB. X-ray diffraction (XRD) confirms the intercalation of AmB in both the MMT-based and LDH-based hybrids. The protective effect of the inorganic layers on the encapsulated AmB avoiding its oxidation and agglomeration is also proven. A release study from the different supports is carried out in simulated wound fluid (SWF) and in Sabouraud Dextrose Broth (SDB) growth medium, showing a sustained release for at least 60 days. Furthermore, in vitro tests were carried out against two causative agents of eumycetoma, Aspergillus flavus and Subramaniula thielavioides species. These results confirmed the capacity of the two layered hybrids to inhibit the growth of both fungal strains, with the LDH-based hybrid showing a stronger growth inhibition effect on A. flavus.