Fabrication and Evaluation of Dissolving Hyaluronic Acid Microneedle Patches for Minimally Invasive Transdermal Drug Delivery by Nanoimprinting
Sayaka Miura, Rio Yamagishi, Mano Ando, Yuna Hachikubo, Ibrahim N. Amirrah, Nur Izzah Md Fadilah, Manira Maarof, Misaki Oshima, Sen Lean Goo, Hiryu Hayashi, Mayu Morita, Mh Busra Fauzi, Satoshi Takei
Abstract
Transdermal drug delivery minimizes pain and provides a controlled, stable release of drugs, but its effectiveness is limited by the skin's natural barriers. Microneedles overcome this problem, enabling minimally invasive drug delivery. Microneedle patches (MNPs) with 80 µm-tall needles composed of hyaluronic acid (HA) were developed and evaluated for their formability, structural integrity, dissolution rate, skin penetration ability, and drug transmission capacity. The influence of the molecular weight of HA on these properties was also investigated. MNPs made from low-molecular-weight HA (30 kDa-50 kDa) demonstrated 12.5 times superior drug permeability in ex vivo human skin compared to needleless patches (NLPs). Furthermore, in the same test, low-molecular-weight HA MNPs had 1.7 times higher drug permeability than high-molecular-weight HA MNPs, suggesting superior transdermal administration. The molecular weight of HA significantly influenced its solubility and permeability, highlighting the potential effectiveness of MNPs as drug delivery systems. Puncture tests demonstrated a penetration depth of 50-60 µm, indicating minimal nerve irritation in the dermis and effective drug delivery to the superficial dermal layer. These results present a manufacturing technique for MNPs incorporating model drug compounds and highlight their potential as a novel and minimally invasive drug delivery method for the biomedical applications of soft gels.