The Anti-Inflammatory Potential of Beclometasone Loaded Filomicelles on Activated Human Monocytes.

Abstract

Polymeric micelles with a hydrophobic core represent versatile nanostructures for encapsulation and delivery of water-insoluble drugs. Here, water-insoluble beclometasone dipropionate (BDP) which is a potent anti-inflammatory therapeutic agent but limited to topical applications so far, was encapsulated. Therefore, we used an amphiphilic block copolymer self-assembling into flexible polymeric filomicelles, which have recently proven to selectively target inflamed areas in patients with inflammatory bowel disease. The small diameter and flexibility of these filomicelles is considered beneficial for transepithelial passages, while their length minimizes the unspecific uptake into non-targeted cells. We successfully established a protocol to load the water-insoluble BDP into the core of the filomicelles, while maintaining the particle stability to prevent any premature drug release. The anti-inflammatory efficacy of BDP-loaded filomicelles was further investigated on LPS-stimulated human monocytes. In these ex vivo assays, the BDP-loaded filomicelles significantly reduce TNF-α, IL-6, IL-1ß, IL-12p70, IL-17a and IL-23 release after 24 h. An additional time course study of drug-loaded filomicelles and their comparison with a common water-soluble and unspecific corticosteroid demonstrated promising results with significant immune response suppression in stimulated monocytes after 2 h and 6 h. These findings demonstrate the potential of polymeric filomicelles as a vehicle for potent water-insoluble corticosteroids. This article is protected by copyright. All rights reserved.