Two-Component Peptidic Molecular Gels for Topical Drug Delivery of Naproxen

Transdermal drug delivery (TDD) is an advantageous and effective approach for the localized delivery of drugs; however, overcoming the high impermeability of the outermost layer of skin, the stratum corneum, represents a significant challenge to TDD. Herein, we describe a simple and biocompatible platform based on a two-component molecular hydrogel for the transdermal delivery of the non-steroidal anti-inflammatory drug (S)-naproxen. The hydrogel is formed by two amphipathic tetrapeptides bearing aromatic side groups and oppositely-charged residues that co-assemble into fibrillar networks at pH 7.4. We demonstrate that (S)-naproxen, which possesses an aromatic region and an ionizable group, can be effectively loaded into the hydrogel. We characterized drug-loaded hydrogels by NMR and rheology and studied in vitro release under physiologically relevant conditions. Moreover, TDD studies on human skin samples demonstrated a twofold increase in the permeation of (S)-naproxen, which could be advantageous for the localized delivery of the drug.

Automated summary

Transdermal drug delivery is an advantageous approach, but the high impermeability of the stratum corneum presents challenges. A two-component molecular hydrogel platform for transdermal delivery of (S)-naproxen was developed, with promising results shown in terms of drug permeation and localized delivery. The study demonstrates an efficient method for enhancing drug delivery through the skin using this hydrogel platform.