Minoxidil-loaded hyaluronic acid dissolving microneedles to alleviate hair loss in an alopecia animal model

Alopecia is defined as hair loss in a part of the head due to various causes, such as drugs, stress and autoimmune disorders. Various therapeutic agents have been suggested depending on the cause of the condition and patient sex, and age. Minoxidil (MXD) is commonly used topically to treat alopecia, but its low absorption rate limits widespread use. To overcome the low absorption, we suggest microneedles (MNs) as controlled drug delivery systems that release MXD. We used hyaluronic acid (HA) to construct MN, as it is biocompatible and safe. We examined the effect of HA on the hair dermal papilla (HDP) cells that control the development of hair follicles. HA enhanced proliferation, migration, and aggregation of HDP cell by increasing cell-cell adhesion and decreasing cell substratum. These effects were mediated by the cluster of differentiation (CD)-44 and phosphorylation of serine‑threonine kinase (Akt). In chemotherapy-induced alopecia mice, topical application of HA tended to decrease chemotherapy-induced hair loss. Although the amount of MXD administered by HA-MNs was 10% of topical treatment, the MXD-containing HA-MNs (MXD-HA-MNs) showed better effects on the growth of hair than topical application of MXD. In summary, our results demonstrated that HA reduces hair loss in alopecia mice, and that delivery of MXD and HA using MXD-HA-MNs maximizes therapeutic effects and minimize the side effects of MXD for the treatment of alopecia. STATEMENT OF SIGNIFICANCE: (1) Significance, This work reports a new approach for treatment of alopecia using a dissolving microneedle (MN) prepared with hyaluronic acid (HA). The HA provided a better environment for cellular functions in the hair dermal papilla cells. The HA-MNs containing minoxidil (MXD) exhibited a significant reduction of hair loss, although amount of MXD contained in them was only 10% of topically applied MXD., (2) Scientific impact, This is the first report demonstrating the direct anti-alopecia effects of HA administrated in a transdermal route and the feasibility of novel therapeutics using MXD-containing HA-MNs. We believe that our work will excite interdisciplinary readers of Acta Biomaterialia, those who are interested in the natural polymers, drug delivery, and alopecia.