Microneedle patch based on dissolving, detachable microneedle technology for improved skin quality - Part 1:ex vivosafety evaluation

Objective 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 +/- 23.5 mu m 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 mu m in length penetrated the epidermis at an averaged depth by 26 mu m 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.