Ionic liquids (ILs) have garnered significant attention in pharmaceutical development because of their diverse applications in improving drug absorption across the nasal mucosa. However, because ILs typically exhibit high viscosity, their poor spray characteristics through intranasal devices pose a challenge for their intranasal administration. To address this issue, we designed an intranasal powder formulation that can be applied using an intranasal powder device by loading an IL within the pores of mesoporous silica (MPS). MPS was added to an IL composed of choline and L-malic acid, and the mixture was stirred. Over time, IR spectroscopy measurements revealed a reduction in the intensity of the IL-derived peaks, suggesting that most ILs were associated with MPS pores. This loading process proceeded more rapidly at higher mixing temperatures owing to the reduced IL viscosity. Furthermore, specific surface area measurements and scanning electron microscopy (SEM) observations demonstrated that the IL was successfully encapsulated within the pores with minimal residue on the MPS surface at an MPS:IL mixing ratio of 1 : 0.4. The IL-MPS prepared from MPS with different physical properties tended to exhibit improved flowability compared to the original MPS, suggesting that the amount of IL retained may vary with the MPS pore volume. The spray characteristics of the IL-MPSs prepared using an intranasal powder device were superior to those of lactose hydrate, a commonly used excipient. Thus, the IL-MPS powder formulation can be a suitable candidate for intranasal administration.

Trichodermamides D–F were isolated in 2017, along with known trichodermamides A–C, from the mangrove-derived endophytic fungus Penicillium janthinellum. Although the pronounced bioactivities of trichodermamides A–C, including cytotoxic and antimicrobial activities, have been reported, the bioactivities of trichodermamides D–F have not yet been determined. The absence of reported lethal activity prompted us to focus on nonlethal biological targets and to conduct enzymatic and phenotypic screening aimed at identifying antivirulence activity. On the other hand, we recently developed a scalable, chiral-pool-based asymmetric synthesis of the trichodermamides A–F. Using this synthetic platform, 11 natural and unnatural enantiomers of trichodermamides D–F, along with selected synthetic intermediates, were evaluated to elucidate structure–activity relationships. This broad screening effort identified that the unnatural enantiomer of trichodermamide F exhibited selective inhibitory activity against the bacterial type III secretion system (T3SS), with an IC₅₀ of 76.7 μM, while showing no antibacterial activity. This study revealed the first trichodermamide derivative that targets the nonlethal T3SS, highlighting the importance of considering unnatural enantiomers and demonstrating the untapped antivirulence potential of the trichodermamide scaffold.

Gelatin is an attractive wall material for microcapsule fabrication because it enables solvent-free processing. However, conventional gelatin microcapsules typically require chemical crosslinkers for structural stabilization, which may raise safety concerns and compromise the bioactivity of encapsulated protein therapeutics or antigens. Herein, we report a crosslinker-free method for fabricating gelatin microcapsules via twin-fluid spray-droplet atomization using a full-cone nozzle. Gelatin microcapsules loaded with ovalbumin (OVA), a model protein (antigen), were successfully prepared without chemical crosslinking, and the encapsulated antigen retained its in vivo antigenicity, indicating that its biological function was preserved.

A practical synthesis of mirabegron, a first-line drug for the treatment of overactive bladder, was developed. This synthetic route avoids the use of structural alerts such as aniline and nitrobenzene, which raise concerns regarding human exposure during large-scale synthesis. This strategy relies on the Cu-catalyzed coupling between an aryl halide and an amide derivative, which was successfully conducted on a gram scale by selecting a suitable diamine ligand and an appropriate protecting group for the amine.