Self-disintegrating protein-leaking microparticles for topical protein delivery

Advanced drug delivery systems, if engineered to enhance drug stability and extend its kinetic bioavailability, are expected to expand the spectrum of local therapeutic approaches for dermatological conditions. In this context, the objective of this study was to explore whether artificial secretory granules, namely nontoxic, microscale granular Zn-assisted protein depots that leak the forming protein in a time-prolonged way, could be suited as functional agents in topical delivery. A model, recombinant form of the human fibroblast growth factor 2 (FGF-2), formulated as secretory granules, promoted efficient tissue repair and wound healing in a rat skin injury model faster than the natural repair process. The kinetic and histological analysis of FGF-2-treated wounds revealed that the package of the protein as secretory granules improves skin regeneration over the soluble version, and that it conduces to a more ordered construction of the extracellular matrix with limited risk of fibrosis. On the other hand, the addition of a claudin-binding peptide (c-CPE) as a fused protein segment slightly delays wound healing but offers functional and histological particularities that modulate the skin regeneration process. Altogether, the data presented here validates this endocrine-like protein drug delivery from synthetic disintegrating protein depots as a powerful and versatile platform for topical application in dermatological disorders.