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.
Microneedles are of great interest in diverse fields, including cosmetics, drug delivery systems, chromatography, and biological sensing for disease diagnosis. Self-dissolving ultrafine microneedles of pure sodium hyaluronate hydrogels were fabricated using a UV-curing TiO2-SiO2 gas-permeable mold polymerized by sol-gel hydrolysis reactions in nanoimprint lithography processes under refrigeration at 5 °C, where thermal decomposition of microneedle components can be avoided. The moldability, strength, and dissolution behavior of sodium hyaluronate hydrogels with different molecular weights were compared to evaluate the suitability of ultrafine microneedles with a bottom diameter of 40 μm and a height of 80 μm. The appropriate molecular weight range and formulation of pure sodium hyaluronate hydrogels were found to control the dissolution behavior of self-dissolving ultrafine microneedles while maintaining the moldability and strength of the microneedles. This fabrication technology of ultrafine microneedles expands their possibilities as a next-generation technique for bioactive gels for controlling the blood levels of drugs and avoiding pain during administration.
Hydrolyzed hyaluronic acid high-resolution fine microneedles of 13 µm in diameter and 24 µm in height were fabricated from hydrolyzed hyaluronic acid gels made in mixtures of water using vacuum environment imprint lithography processes with a water permeable mold. The gas traps of water and volatile solvents in the imprint materials cause transfer failure in the conventional water impermeable molds of quartz and metal. However, the water permeable mold allows the use of 67 wt% dilution water with high solubility to increase the fluidity of the hydrolyzed hyaluronic acid during the patterning of high-resolution fine microneedles for cosmetics and pharmaceuticals. This demonstration sets a new paradigm of functional pure gels for high-resolution nano-patterning applications with various cosmetic and pharmaceutical materials containing dilution water using a water permeable mold.
This study presents the development of photolithography employing biomass-based resist materials derived from polyglucuronic acid. Traditional resist materials require coating and developing procedures involving organic solvents, whereas our approach enables the use of water-based spin-coating and developing processes. The water-soluble biomass resist material, derived from polyglucuronic acid, exhibited exceptional photosensitivity at an exposure wavelength of 365 nm and a dose of approximately 90 mJ/cm2. We successfully patterned the microstructures, creating 3 µm lines and 6 µm holes. This organic solvent-free coating process underscores its applicability in scenarios such as in the microfabrication on plastic substrates with limited organic solvent tolerance and surface-patterning biomaterials containing cells and culture components.
We attempted to perform surface microfabrication of the bioabsorbable material lactic acid–glycolic acid copolymer (LG-80) using a micro-imprint lithography technique with a gas-permeable porous mold at less than 5 °C. As a result, high-resolution surface micromachining with a height of 1.26 μm and a pitch of 2.97 μm was achieved using a convex sapphire mold with a height of 1.3 μm and a pitch of 3 μm. After processing, the LG-80 exhibited high water repellency, and FT-IR analysis of the surface showed no significant change in its chemical structure, confirming that the surface microfabrication was successful, while retaining the properties of the material. This demonstrated new possibilities for surface microfabrication technology for bioabsorbable materials, which are expected to be applied in the medical and life science fields in products such as surgical implants, tissue regeneration materials, and cell culture scaffold materials. In particular, the use of micro-imprint lithography enables low-cost and high-precision processing, which will be a major step toward the practical application of bioabsorbable materials.
Cationic gas-permeable molds fabricated via sol–gel polymerization undergo cationic polymerization using epoxide, resulting in gas permeability owing to their cross-linked structures. By applying this cationic gas-permeable mold to nano-injection molding, which is used for the mass production of resins, nano-protrusion structures with a height of approximately 300 nm and a pitch of approximately 400 nm were produced. The molding defects caused by gas entrapment in the air and cavities when using conventional gas-impermeable metal molds were improved, and the cationic gas-permeable mold could be continuously fabricated for 3000 shots under non-vacuum conditions. The results of the mechanical evaluations showed improved thermal stability and Martens hardness, which is expected to lead to the advanced production of resin nano-structures. Furthermore, the surface roughness of the nano-protrusion structures fabricated using injection molding improved the water contact angle by approximately 46°, contributing to the development of various hydrophobic materials in the future.