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, the contribution of AF to skin bio‐adhesivity aiming toward topical treatments is investigated. Liquid crystalline mesophase (LCM) based on phytantriol is formulated, with the aqueous phase containing either water or a solution of 4 wt% amyloid fibrils. Then resveratrol is added as a model anti‐inflammatory molecule. The developed LCM presents a double gyroid Ia3d mesophase. The incorporation of AF into the LCM increases its bio‐adhesive properties. In vitro release and ex vivo permeation and retention confirm the controlled release property of the system, and that resveratrol is retained in epidermis and dermis, but is also permeated through the skin. All formulations are biocompatible with L929 cells. The in vivo assay confirms that systems with AF lead 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. Amyloid fibrils are stable aggregates that mimic the extracellular matrix and are a potent scaffold for cells. The incorporation of amyloid fibrils in topical drug delivery systems, such as liquid crystalline mesophases, increases their bio‐adhesive properties, solving the problem of fluidity of topical formulations and enhancing the treatment of topical diseases.