Microneedles (MNs) are a new system of effective drug delivery that create micron-sized pathways to the epidermis or upper dermis regions of the skin. In this study, we developed coated-type microneedles for direct hispidin delivery to the skin. Hispidin is a well-known plant-derived antioxidant component showing antitumor, anti-inflammatory, antiallergic, antiangiogenic, antioxidant, hypoglycemic, hypolipidemic, and immunomodulatory activities. Polymeric blends of polylactic acid (PLA) and polycaprolactone (PCL) were casted as MNs to enhance skin permeability. PLA/PCL MNs exhibited the highest strength of 51.26 MPa with a width of ~200 ųm. Hispidin was directly coated onto the MNs with PLA/PCL blends to form delivery layers. Compared to the hispidin-only delivery layer, skin permeability of hispidin increased by over 50% when using agarose gel in in vitro tests. In a dose-dependent manner, hispidin coated on PLA/PCL MNs also showed a brightening effect, as well as anti-inflammatory activity at the gene and protein level in skin cell culture experiments. It also demonstrated antimicrobial activity, and showed no cytotoxicity to skin cells. These results suggest that the PLA/PCL MN system with hispidin may have great potential as a prototype platform for various drug delivery systems, allowing the development of more effective subcutaneous delivery of vaccines, oligonucleotides, insulin, and many other cosmetic applications.

Sulforaphane increases the expression of the dihydrotestosterone (DHT)-degrading enzyme, 3α-hydroxysteroid dehydrogenase (3α-HSD) in the liver, which accelerates DHT degradation, thereby inhibiting hair loss in the animal model. In this study, we elucidated its underlying mechanism and demonstrated that sulforaphane has hair loss inhibitory functions in RAW264.7 macrophage cells and Hepa1c1c7 cells at the cellular and gene levels. The gene expression level of an isoform of 3α-HSD, Akr1c2, increased in a dose-dependent manner when these cells were treated with sulforaphane, but there were no significant differences at the gene levels of Akr1c2 and Dhrs9 for the negative control mixture of biotin, dexpanthenol, and L-menthol. These studies indicated that sulforaphane is involved in regulating the gene expression of Akr1c2. To further determine whether this hair product has effects on alleviating hair loss symptoms, clinical trials were also conducted for 18 weeks. We performed a visual evaluation of the parietal and frontal lines of 23 patients before and after using the product, and then calculated the total number of hairs. This clinical study showed that the parietal lines and bangs visually improved and the number of hairs increased by 6.71% from before using the test product to 18 weeks after using the test product. Taken together, these cellular and clinical studies strongly suggest that sulforaphane may be an active ingredient that significantly alleviates hair loss symptoms.

The main challenges in developing zeolites as cosmetic drug delivery systems are their cytotoxicities and the formation of drug-loading pore structures. In this study, Au-decorated zeolite nanocomposites were synthesized as an epidermal delivery system. Thus, 50 nm-sized Au nanoparticles were successfully deposited on zeolite 13X (super cage (α) and sodalite (β) cage structures) using the Turkevich method. Various cosmetic drugs, such as niacinamide, sulforaphane, and adenosine, were loaded under in vitro and in vivo observations. The Au-decorated zeolite nanocomposites exhibited effective cosmetic drug-loading efficiencies of 3.5 to 22.5 wt% under various conditions. For in vitro cytotoxic observations, B16F10 cells were treated with various cosmetic drugs. Niacinamide, sulforaphane, and adenosine-loaded Au-decorated zeolite nanocomposites exhibited clear cell viability of over 80%. Wrinkle improvement and a reduction in melanin content on the skin surface were observed in vivo. The adenosine delivery system exhibited an enhanced wrinkle improvement of 203% compared to 0.04 wt% of the pure adenosine system. The niacinamide- and sulforaphane-loaded Au-decorated zeolite nanocomposites decreased the skin surface melanin content by 123% and 222%, respectively, compared to 2 and 0.01 wt% of pure niacinamide and sulforaphane systems, respectively. As a result, Au-decorated zeolite nanocomposites show great potential as cosmetic drug epidermal delivery systems for both anti-aging and lightening effects.