Amyloid Fibrils Enhance the Topical Bio-Adhesivity of Liquid Crystalline Mesophase-Based Drug Formulations.

Despite their distinctive secondary structure based on cross β-strands, amyloid fibrils (AF) are stable fibrous protein aggregates with features similar to collagen, one of the main components of the extracellular matrix, and thus constitute a potential scaffold for enhancing cell adhesion for topical applications. Here we investigate the contribution of AF to skin bio-adhesivity aiming towards topical treatments. We formulated liquid crystalline mesophase (LCM) based on phytantriol, with the aqueous phase containing either water or a solution of 4 wt% amyloid fibrils. We then added resveratrol as a model anti-inflammatory molecule. The developed LCM presented a double gyroid Ia3d mesophase. The incorporation of AF into the LCM increased its bio-adhesive properties. In vitro release and ex vivo permeation and retention confirmed the controlled release property of the system, and that resveratrol was retained in epidermis and dermis, but also permeated through the skin. All formulations were biocompatible with L929 cells. The in vivo assay confirmed that systems with AF led to a higher anti-inflammatory effect of resveratrol. These results confirm the hypothesis that the incorporation of AF in the LCM increases the bio-adhesiveness and efficiency of the system for topical treatment, and consequently, the therapeutical action of the encapsulated drug. This article is protected by copyright. All rights reserved.