Organic molecules can absorb light energy to form excited states, from which various photophysical and photochemical processes such as heat, emission, and chemical reactions occur during deactivation to ground states. Therefore, it is highly important to control molecular properties in the excited states in many scientific fields including pharmaceutical sciences. Especially, the author has focused on the development of molecular technologies to utilize near-IR light, showing deep tissue penetration favorable for biomedical applications. The author has designed and synthesized 18π-electron tautomeric hydroxybenziphthalocyanines as functional near-IR-light-absorbing compounds with tunable aromaticity. Their near-IR absorption can be controlled by external stimuli such as chemical modifications and solvent effects. Additionally, the benziphthalocyanines were utilized for activatable near-IR photoacoustic imaging probes owing to their nonradiative thermal deactivation processes. The author also succeeded in developing a redox-switchable near-IR dye called benzitetraazaporphyrin. This molecule exhibits strong near-IR absorption in the 20π-electron antiaromatic reduced structure, while the 18π-electron oxidized structure is near-IR silent. The benzitetraazaporphyrin would be useful as near-IR probes working in reductive environments such as cancer cells.

In vitro studies using human liver-derived cell lines have been investigated as a method for evaluating biliary excretion of drugs. In several of these studies, it has been shown that a capillary bile duct-like network is formed by culturing liver-derived cells in two/three-dimensional culture (2D and/or 3D) using fluorescent substrates that are excreted in bile. Recently, it was reported that bile duct epithelial-like cells (BECs) capable of long-term proliferation can be obtained by establishing organoids from primary human hepatocytes. We therefore cultured these bile duct epithelial-like organoids on an insert in 2D culture and investigated the biliary excretory capacity of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated protein2 (MRP2) substrates. We found that all drugs were significantly excreted into the bile duct lumen side. In the first half of this review, the current state of knowledge on biliary excretion of drugs is summarized, and in the second half, the latest findings, including our presentation at the Annual Meeting Symposium of The Pharmaceutical Society of Japan in 2024, are described, focusing on the evaluation system for biliary excretion of drugs.

To increase success rates of clinical studies, preclinical evaluation systems have been expected to improve human predictability. In addition, future preclinical studies need to become more sophisticated and efficient on the back ground of the adoption of FDA Modernization Act 2.0 and the 3R principle promotion of animal tests. In this review, we will discuss about the efficiency of in vivo imaging in preclinical studies taking ‘an attempt to establishment of in vitro in vivo extraporation (IVIVE) model for seizure risk assessment using microphysiological system (MPS) and magnetic resonance imaging (MRI)’, and ‘an attempt to predict drug delivery to the alveoli’ as examples. In the seizure risk assessment of new drugs so far, primary cultures of rodent neurons and in vivo behavioral observation have been mainly used, however, since the human induced pluripotent stem cell (iPSC) technology was reported, the need for IVIVE model is more and more increasing to improve human predictability. As an MPS, we here introduce microelectrode array (MEA) system recording of primary culture of rodent neurons, while as in vivo experiments, we here introduce the measurement of cerebrospinal fluid (CSF) concentrations and MRI imaging of forebrains of the rats i.p. injected with seizurogenic compounds. In case of inhalation drugs, it has been difficult to confirm whether or not the drugs surely reach alveoli. We visualized two-dimensional spatial localization of inhaled ciclesonide (CIC) in rat lungs after administration of a single dose of a CIC aerosol using by desorption electrospray ionization-time of flight mass spectrometry imaging (DESI-MSI).

Non-clinical pharmacological safety studies are conducted using cells and animals to ensure the safety of pharmaceuticals in humans. Following these studies, drug candidates are administered to humans during clinical trials. Safety must be sufficiently confirmed in non-clinical studies to ensure that test participants suffer no adverse health effects. However, due to species differences, low ability to extrapolate from in vitro to in vivo evaluation methods, and other problems, health hazards may unfortunately still occur. Therefore, sophisticated in vitro evaluation systems using human cells are actively being pursued. The main challenge remains the lack of a reliable methodology for extrapolating in vitro results to in vivo settings. We have attempted to extract parameters that can be predictably translated from in vitro [contractile evaluation in three-dimensional (3D) heart tissue] to in vivo (guinea pig echocardiography) conditions, using cardiac contractile dysfunction induced by anticancer drugs as an example. In this review, we introduce the in vitro methods developed to date to evaluate this cardiac contractile dysfunction, analyze the factors enabling highly accurate prediction of torsades de pointes in humans based on past proarrhythmic risk prediction methods using human induced pluripotent stem cell-derived cardiomyocytes, and apply them to evaluate cardiac contractile dysfunction caused by anticancer drugs using three-dimensional heart tissue. We also introduce the proposed strategy for this evaluation method in this section.

In this study we have developed a method of profiling multiple “single-molecules” of enzymes in biological samples, by studying their activities as a form of single-molecule enzyme activity assay. The original method for single-molecule enzyme assay in microfabricated chamber devices was reported many years ago, but we for the first time report the application of this concept to identifying each enzyme in the chamber by simultaneously measuring activities against multiple substrates. Based on this idea, we developed the protein profiling technique to globally detect and “count” different sets of enzymes in biological samples containing various characterized and uncharacterized enzymes. We expect that the methodology will open up the application of single-molecule enzyme assay to discovering and using novel biomarker proteins.

Antibody therapeutics have become a major modality for cancer treatment. Particularly, immune checkpoint inhibitors have shown remarkable efficacy against various cancers. However, similar to other antibody therapeutics, they have not demonstrated clinical efficacy against malignant brain tumors. The primary reason for this is the presence of the blood–brain tumor barrier (BBTB) in the endothelial cells of malignant brain tumors, which prevents antibodies from entering the tumor parenchyma. Additionally, treatment with immune checkpoint inhibitors is clinically challenged by the occurrence of immune-related adverse events (irAEs) owing to non-specific and excess activation of the immune system. To address these issues, we integrated synthetic polymer-based drug delivery systems with immune checkpoint inhibitors. Specifically, we modified anti-PD-L1 antibodies with multiple glucosylated poly(ethylene glycol) (PEG) chains via disulfide bonds. This glucose–PEG-conjugated anti-PD-L1 antibody effectively accumulates in glioblastoma by penetrating the BBTB through the interaction of glucose ligands with glucose transporter-1, which is overexpressed in glioblastoma endothelial cells. Subsequently, the PEG chains detach from the antibodies in response to the reductive environment within the glioblastoma, thereby blocking PD-L1 expression. Conversely, the PEG chains remain conjugated to antibodies in the bloodstream and normal tissues, masking their functions. The glucose–PEG-conjugated anti-PD-L1 antibody demonstrated significant efficacy against glioblastoma, while reducing the risk of irAEs in normal tissues. This technology is applicable to various antibody therapeutics and can be adapted to target other organs or specific cell types by exchanging ligand molecules, offering broad potential therapeutic applications.

Bio-related nanoparticles are key players in intercellular communication and represent the ultimate goal of nanotechnology as material-transport systems. Biological membranes support the functionality of bio-related nanoparticles; therefore, understanding the correlation between membrane molecular characteristics and the functions of bioparticles is essential. In this study, we developed foundational technologies for measuring the biological membranes of bioparticles by integrating fields such as separation science, materials chemistry, and omics. Furthermore, we developed a new methodology for incorporating the functions of natural bioparticles into artificial nanomaterials.

I graduated from the Faculty of Pharmacy and then worked in the Faculty of Medicine, and my research has always focused on applying basic research to clinical practice. I first encountered purine metabolism research when I worked at the Teikyo University School of Medicine. I completed my doctoral studies by applying the measurement of 5′-methylthioadenosine (MTA), a source of adenine, to clinical cases. As part of research into hyperuricemia and gout, which are related to purine metabolism, we established a method for measuring the purine content in foods and reported the amounts of purine in many foodstuffs together with previous values. That research project was largely due to the dedication of students working on their graduation research after moving to the Faculty of Pharmacy. The resulting analytical data are included in treatment guidelines for hyperuricemia and gout, and are used as reference values in lifestyle guidance, especially dietary therapy, for actual patients. Furthermore, we performed micro-analysis of urinary stones, which are a common complication in patients with hyperuricemia and gout. In urinary stones, proteins related to inflammation and immunity were commonly detected, as well as proteins that differed depending on the type of stone, indicating different formation processes. I hope that the results of these research projects can be used to benefit society.

LM1010, a high-performance liquid chromatography system for therapeutic drug monitoring (TDM) of various agents in clinical practice, is currently approved in Japan. Unlike conventional systems, LM1010 can rapidly measure clinical samples, and data analysis is based on the absolute calibration curve method and fully automated. However, the analytical performance of the LM1010 for the measurement of serum concentrations of linezolid (LZD) has not yet been evaluated. In this study, we aimed to evaluate the analytical performance of LM1010 and confirm the long-term stability of LZD at −30°C. One hundred forty-eight serum samples were collected from 25 patients (17 men and 8 women) who received LZD. Serum concentrations of LZD were measured using LM1010 and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Three LM1010 instruments were used to confirm the differences in the measured values. A Passing–Bablok regression analysis demonstrated a strong correlation between LM1010 and LC-MS/MS (r=0.991), and comparable results were observed among the three LM1010 instruments (r=0.982–0.998). Bland–Altman analyses revealed that the average difference between LM1010 and LC-MS/MS methods was 1.7%, and similar results were observed among the three LM1010 instruments. The long-term stability of serum LZD in samples stored at −30°C for 48 weeks was also confirmed. These results suggest that LM1010 can be used for TDM of LZD in clinical practice.

This study evaluated the educational impact of dental seminars involving practicing pharmacists and dentists on pharmacy students. Its primary objective was to assess changes in learning attitudes and improvements in oral care knowledge through lectures and group discussions. The dental seminars were conducted during October–November 2024, and participants included 14 second-year pharmacy students. Participants completed surveys before and after the seminars that addressed topics such as “antibiotics in dental care” and “pharmacist–dentist collaboration.” Survey results indicated that the proportion of students recognizing the relationship between pharmacy and dentistry increased from 71.5 to 100%. Furthermore, the percentage of students who expressed a desire to learn more about dentistry increased from 42.9 to 85.7%. Knowledge assessments revealed significant improvements in the understanding of appropriate use of antibiotics for tooth extraction and oral care during cancer therapy. However, no improvement was observed in foundational knowledge of dental anatomy, underscoring the necessity of reinforcing basic education. This study provided preliminary insights into the effectiveness of incorporating dental education into the pharmacy curricula. These findings can contribute to the development and refinement of educational programs at other universities and institutions.