Strategy for hypertrophic scar therapy: Improved delivery of triamcinolone acetonide using mechanically robust tip-concentrated dissolving microneedle array

Abstract

A hypertrophic scar (HS) is a cutaneous condition characterized by deposits of excessive amounts of collagen that produces a raised scar, causing physical, psychological, and cosmetic problems for the patient. The therapeutic efficacy of conventional transdermal drug delivery systems is often limited because the HS tissue is more compact than normal skin. At present, intralesional multi-injection of triamcinolone acetonide (TA) using a syringe is one of the most commonly used treatments for HS. However, the efficacy of this treatment is highly dependent on the skill of the medical professionals administering the injection. Even with co-administration of local anesthetics, traditional injection still causes pain to the patients, resulting in poor compliance. The purpose of this study was to provide an alternative treatment for HS by establishing a novel intradermal delivery system with a dissolving microneedle array (DMNA). To produce needles of higher mechanical strength for successful insertion into the compact and hard HS tissue, hydroxypropyl-β-cyclodextrin (HP-β-CD) was added into sodium hyaluronic acid (HA), the needle material. The hydrogen interaction between HP-β-CD and HA restricted the mobility of the molecular chains, and subsequently increased the elastic modulus of the complex materials. The HP-β-CD also contributed to improved loading of the hydrophobic drug molecules into the DMNA needle tips. To assess the delivery of TA to the HS site via DMNA, an HS model was established in the ventral skin of New Zealand rabbits' ears. It was found that the value of the scar elevation index was decreased to normal, together with the down regulation of mRNA expressions of Collagen I and transforming growth factor-β1 (TGF-β1) following the administration of DMNA containing TA (TA-DMNA). Western blotting results also revealed decreased protein expressions of both Collagen I and TGF-β1. Hence, TA-DMNA appears to be a promising alternative to multi-injection of TA injection, providing a convenient and low-pain therapeutic strategy for HS treatment.