Objective Microneedle patches based on dissolving, detachable microneedle technology (Russian patent No. 2652567; US patent EFS No. 32735812; WO/2019/231360) are novel dermatological products that allow safe, painless and effective reduction of epidermal wrinkles after six procedures. The purpose of this study was two‐fold (a) to assess the safety and efficacy of microneedle patches comprising 650 microneedles containing hyaluronic and ferulic acids after 6 procedures of applying the applicator to the skin for 25 min; and (b) to correlate our previously reported ex vivo findings. Methods The microneedle applicator contains 650 microneedles, which dissolve in 25 min of exposure. The effectiveness of microneedle applicators was confirmed by a randomized split‐phase study involving 82 subjects. Applications of microneedle patches were performed at intervals of two times per week, and the effectiveness was assessed at 6 weeks after the start of the study. Results The results of the profilometric evaluation of skin smoothness demonstrated a significant reduction in the average roughness index by 65.32 ± 2.99% and in the mean skin waviness by 66.84 ± 1.6% compared with these indicators in the control group (P < 0.05). The therapeutic effect of the procedure was confirmed by an ultrasound examination that registered a 72.2 ± 5.4% and 25 ± 1.4% increase in echo‐density of the epidermis and dermis, respectively. An independent blinded skin evaluation by dermatologists revealed steady decrease in puffiness of the application area in 89.9% of patients, increased elasticity in 78.3% of the patients, and reduced severity of epidermal wrinkles in 89.9% of the patients. Conclusions The applicator with 650 soluble microneedles on its surface containing hyaluronic and ferulic acids is considered a safe, effective and convenient way to improve the skin quality in the periorbital region after six procedures. Nevertheless, additional studies of soluble microneedles are required to fully assess the amount and distribution area of the injected hyaluronic acid and other active components, as well as to detail the mechanism of action of soluble microneedles to improve skin quality.

The aim of the paper presented herein is the description and safety evaluation of the process of dissolution of an 86-microneedle patch composed of hyaluronic acid, when applied topically to human abdominal skin explants. Such explants were chosen to replace the inability of obtaining periorbital skin. In order to evaluate penetration and dissolution of the microneedles, we employed histochemical methods and a fluorescent dye FITC (fluorescein isothiocyanate). METHODS: Abdominoplasty human skin explants were treated with square microneedle patches with a 1.5-cm 2 surface area, containing 86 microneedles and having 450 AE 23.5 µm in height with 1 mm interspacing between nearest neighbouring microneedles. Histological processing and staining for cell viability, FITC distributions and glycosaminoglycans were performed. The stained surface percentage for each treatment was compared to control untreated samples at given time points. A Mann-Whitney test was used to identify the difference between two populations (sites of skin samples punctured with stained and clear microneedles, respectively) at the given level of statistical significance (P < 0.05). RESULTS: The application of the MN patch to excised skin explants showed these microneedles to be non-invasive into the dermis of the skin. Skin puncturing with MN patches revealed 17 different sites of microneedle penetration immediately afterwards and 4 sites, 2 h later. Although there were some variances in the epidermal depth of penetration, these variances did not impact on cell viability. The hyaluronic acid-based microneedles having 450 µm in length penetrated the epidermis at an averaged depth by 26 µm without disrupting skin cell viability and without causing an inflammatory response. Hyaluronic acid could be detected in most of these penetration sites, with no diffusion into the dermis, which is important for cosmetic applications. FITC analysis uncovered fluorescein isothiocyanate distribution within microneedle insertion site, which remained steady after 2 and 6 h of experimentation. CONCLUSION: Using ex vivo tracer staining studies, we have shown that the evaluated microneedle applicator is capable of penetrating the skin epidermis and delivering substances embedded in the needle polymer matrix. In addition, the tested product was shown to be safe, which provides a broad perspective for delivering cosmetic and pharmaceutic agents.