Fabrication Technology of Self-Dissolving Sodium Hyaluronate Gels Ultrafine Microneedles for Medical Applications with UV-Curing Gas-Permeable Mold.

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.

Characterization of Rickets Type II Model Rats to Reveal Functions of Vitamin D and Vitamin D Receptor.

Vitamin D has been known to exert a wide range of physiological effects, including calcemic, osteogenic, anticancer, and immune responses. We previously generated genetically modified (GM) rats and performed a comparative analysis of their physiological properties to elucidate the roles of vitamin D and vitamin D receptor (VDR). In this study, our primary goal was to investigate the manifestations of type II rickets in rats with the VDR(H301Q) mutation, analogous to the human VDR(H305Q). Additionally, we created a double-mutant rat with the VDR(R270L/H301Q) mutation, resulting in almost no affinity for 1,25-dihydroxy-vitamin D3 (1,25D3) or 25-hydroxy-vitamin D3 (25D3). Notably, the plasma calcium concentration in Vdr(R270L/H301Q) rats was significantly lower than in wild-type (WT) rats. Meanwhile, Vdr(H301Q) rats had calcium concentrations falling between those of Vdr(R270L/H301Q) and WT rats. GM rats exhibited markedly elevated plasma parathyroid hormone and 1,25D3 levels compared to those of WT rats. An analysis of bone mineral density in the cortical bone of the femur in both GM rats revealed significantly lower values than in WT rats. Conversely, the bone mineral density in the trabecular bone was notably higher, indicating abnormal bone formation. This abnormal bone formation was more pronounced in Vdr(R270L/H301Q) rats than in Vdr(H301Q) rats, highlighting the critical role of the VDR-dependent function of 1,25D3 in bone formation. In contrast, neither Vdr(H301Q) nor Vdr(R270L/H301Q) rats exhibited symptoms of alopecia or cyst formation in the skin, which were observed in the Vdr-KO rats. These findings strongly suggest that unliganded VDR is crucial for maintaining the hair cycle and normal skin. Our GM rats hold significant promise for comprehensive analyses of vitamin D and VDR functions in future research.