Self-assembled nanostructures of L-ascorbic acid alkyl esters support monomeric amphotericin B

Abstract

Hypothesis Amphotericin B (AmB) is a highly effective antimicrobial, with broad antimycotic and antiparasitic effect. However, AmB poor water-solubilisation and aggregation tendency limits its use for topical applications. We studied the capacity of nanostructures formed by alkyl esters of L-ascorbic acid (ASCn) to solubilise AmB and tested the relationship between the prevalence of the monomeric form of AmB and its effectiveness as antimicrobial agent. Experiments We developed self-assembled nanostructures formed by the commercial compound, palmitoyl ascorbic acid, as well as the shorter chained myristoyl and lauroyl ascorbic acid. AmB loaded ASCn nanostructures were studied by a combination of spectroscopic techniques, together with particle analysis, differential scanning calorimetry, microbiological tests, and Langmuir monolayer visualisation. Findings We found no direct relation between the antimicrobial capacity and the prevalence of the monomeric form of the drug. However, the later was related to chemical stability and colloidal robustness. Nanostructures formed by ASC16 in its anionic state provide an appropriate environment for AmB in its monomeric form, maintaining its antimicrobial capacity. Langmuir film visualisation supports spectrophotometric evidence, indicating that ASC16 allows the in-plane solubilisation of AmB. Coagels formed by ASC16 appear as promising for carrying AmB for dermal delivery.