Self-Assembled Amphotericin B Pharmacosome-Like Vesicles Derived from Lipid-Based Microtubes: A Model Carrier to Further Explore

Abstract

Background: Self-assembled drug delivery systems are of much interest since they can be produced by simple low cost and solvent-free procedures. Pharmacosomes are supramolecular-structured nanocarriers with benefits for drug stability and targeting delivery. Amphotericin B (AmB) still remains an important agent for the treatment of invasive mold infections, e.g invasive aspergillosis, although the challenge for new formulations is still prevailing due to high rates of toxicity. Objective: We have previously reported the incorporation of AmB into 12-hydroxystearic acid lipid-based microtubes (MTs) for topical use, herein we report the ability of AmB-MTs to self-assemble into vesicles upon dilution. Methods: AmB-MTs with different drug concentration (1, 3, 5 mg/ml) were prepared and size determination was carried out for different dilutions. Morphology was evaluated by microscopy. In vitro cytotoxicity was evaluated in Vero cells and in vitro activity against Aspergillus fumigatus and Aspergillus flavus was assessed. Results: AmB-MTs closed upon dilution to form vesicles ranging from 200 nm to 1µm. AmB MIC (Minimun inhibitory concentration) for both Aspergillus species was 0.0625 and 0.125 µg/ml for dispersion and reconstituted lyophilized, respectively. Conclusion: AmB pharmacosome-like vesicles are smaller structures than MTs may thus be favourable for other delivery routes. We assume that this kind of pharmacosomes-like carrier is a promising model for the obtention of new vesicular carriers based on lipid MTs.