Advanced Pharmaceutical Science and Technology in Japan (Closed)

Editors

Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, Japan
Interests: drug delivery system; lipid nanoparticle; lipid synthesis; microfluidics; short interfering RNA; mRNA; genome editing
Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan
Interests: drug delivery system; nucleic acid drugs; extracellular vesicles; exosomes

Topical Collection Information

Dear Colleagues,

Japanese researchers are dedicated to promoting advancements in pharmaceutical sciences and technology. Hence, Japan continues to have significant impact on the research field. In addition, recent notable progress on pharmaceutical applications of nanomaterials and nanotechnology have been made, in particular, the drug delivery of macromolecules, including RNAs (e.g., siRNAs, miRNAs, antisense oligonucleotides, and mRNAs), DNAs, proteins, and peptides as well as small molecule drugs. This topical collection will highlight the research within pharmaceutical sciences and technology that is currently ongoing in Japan, both within academic and industrial institutions, especially in the following pioneering topics: novel formulation design, drug delivery, polymer science, material science, pharmacokinetics, drug metabolism, drug transport, manufacturing science, and biotechnology. In doing so, we wish to share and extend upon the pharmaceutical expertise and advancements in pharmaceutical sciences in Japan.

This will be achieved by presenting a topical collection of research papers and review articles covering the recent progress and achievements in high-end pharmaceutical science.

Dr. Yusuke Sato
Prof. Dr. Yoshinobu Takakura
Collection Editors

Manuscript Submission Information

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Keywords

  • formulation design
  • drug delivery
  • polymer science
  • materials science
  • pharmacokinetics
  • drug metabolism and drug transport
  • manufacturing science
  • biotechnology

Related Special Issue

Published Papers (9 papers)

2022

Jump to: 2021

17 pages, 2585 KiB  
Article
Processing Parameters and Ion Excipients Affect the Physicochemical Characteristics of the Stereocomplex-Formed Polylactide-b-Polyethylene Glycol Nanoparticles and Their Pharmacokinetics
by Kohei Ogawa, Hidemasa Katsumi, Yasushi Moroto, Masaki Morishita and Akira Yamamoto
Pharmaceutics 2022, 14(3), 568; https://doi.org/10.3390/pharmaceutics14030568 - 04 Mar 2022
Cited by 3 | Viewed by 2129
Abstract
To optimize the characteristics of stereocomplex polylactide-b-polyethylene glycol nanoparticles (SC-PEG NPs) in terms of pharmacokinetics (PK), we chose continuous anti-solvent precipitation with a T-junction as a preparation method and investigated the effect of using solvents containing an ion excipient (lithium bromide, LiBr) on [...] Read more.
To optimize the characteristics of stereocomplex polylactide-b-polyethylene glycol nanoparticles (SC-PEG NPs) in terms of pharmacokinetics (PK), we chose continuous anti-solvent precipitation with a T-junction as a preparation method and investigated the effect of using solvents containing an ion excipient (lithium bromide, LiBr) on the characteristics of SC-PEG NPs by changing the processing temperature and total flow rate (TFR). Processing temperatures above the melting temperature (Tm) of the PEG domain produced a sharper polydispersity and denser surface PEG densities of SC-PEG NPs than those produced by processing temperatures below the Tm of the PEG domains. Response surface analysis revealed that a higher LiBr concentration and slower TFR resulted in larger and denser hydrodynamic diameters (Dh) and surface PEG densities, respectively. However, a high concentration (300 mM) of LiBr resulted in a decreased drug loading content (DLC). 14C-tamoxifen-loaded 111In-SC-PEG NPs with larger Dh and denser surface PEG densities showed a prolonged plasma retention and low tissue distribution after intravenous injection in mice. These results indicate that the novel strategy of using solvents containing LiBr at different processing temperatures and TFR can broadly control characteristics of SC-PEG NPs, such as Dh, surface PEG densities, and DLC, which alter the PK profiles and tissue distributions. Full article
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14 pages, 2827 KiB  
Article
Long-Acting Thioredoxin Ameliorates Doxorubicin-Induced Cardiomyopathy via Its Anti-Oxidative and Anti-Inflammatory Action
by Ryota Murata, Hiroshi Watanabe, Hiroto Nosaki, Kento Nishida, Hitoshi Maeda, Motohiro Nishida and Toru Maruyama
Pharmaceutics 2022, 14(3), 562; https://doi.org/10.3390/pharmaceutics14030562 - 03 Mar 2022
Cited by 4 | Viewed by 2016
Abstract
Although the number of patients with heart failure is increasing, a sufficient treatment agent has not been established. Oxidative stress and inflammation play important roles in the development of myocardial remodeling. When thioredoxin (Trx), an endogenous anti-oxidative and inflammatory modulator with a molecular [...] Read more.
Although the number of patients with heart failure is increasing, a sufficient treatment agent has not been established. Oxidative stress and inflammation play important roles in the development of myocardial remodeling. When thioredoxin (Trx), an endogenous anti-oxidative and inflammatory modulator with a molecular weight of 12 kDa, is exogenously administered, it disappears rapidly from the blood circulation. In this study, we prepared a long-acting Trx, by fusing human Trx (HSA-Trx) with human serum albumin (HSA) and evaluated its efficacy in treating drug-induced heart failure. Drug-induced cardiomyopathy was created by intraperitoneally administering doxorubicin (Dox) to mice three times per week. A decrease in heart weight, increased myocardial fibrosis and markers for myocardial damage that were observed in the Dox group were suppressed by HSA-Trx administration. HSA-Trx also suppressed the expression of atrogin-1 and myostatin, myocardial atrophy factors in addition to suppressing oxidative stress and inflammation. In the Dox group, a decreased expression of endogenous Trx in cardiac tissue and an increased expression of macrophage migration inhibitory factor were observed, but these changes were restored to normal levels by HSA-Trx administration. These findings suggest that HSA-Trx improves the pathological condition associated with Dox-induced cardiomyopathy by its anti-oxidative/anti-inflammatory and myocardial atrophy inhibitory action. Full article
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16 pages, 1096 KiB  
Review
Iontophoresis of Biological Macromolecular Drugs
by Mahadi Hasan, Anowara Khatun and Kentaro Kogure
Pharmaceutics 2022, 14(3), 525; https://doi.org/10.3390/pharmaceutics14030525 - 26 Feb 2022
Cited by 12 | Viewed by 3334
Abstract
Over the last few decades, biological macromolecular drugs (e.g., peptides, proteins, and nucleic acids) have become a significant therapeutic modality for the treatment of various diseases. These drugs are considered superior to small-molecule drugs because of their high specificity and favorable safety profiles. [...] Read more.
Over the last few decades, biological macromolecular drugs (e.g., peptides, proteins, and nucleic acids) have become a significant therapeutic modality for the treatment of various diseases. These drugs are considered superior to small-molecule drugs because of their high specificity and favorable safety profiles. However, such drugs are limited by their low oral bioavailability and short half-lives. Biological macromolecular drugs are typically administrated via invasive methods, e.g., intravenous or subcutaneous injections, which can be painful and induce needle phobia. Noninvasive transdermal delivery is an alternative administration route for the local and systemic delivery of biological macromolecular drugs. However, a challenge with the noninvasive transdermal delivery of biological macromolecular drugs is the outermost layer of the skin, known as the stratum corneum, which is a physical barrier that restricts the entry of extraneous macromolecules. Iontophoresis (IP) relies on the application of a low level of electricity for transdermal drug delivery, in order to facilitate the skin permeation of hydrophilic and charged molecules. The IP of several biological macromolecular drugs has recently been investigated. Herein, we review the IP-mediated noninvasive transdermal delivery of biological macromolecular drugs, their routes of skin permeation, their underlying mechanisms, and their advance applications. Full article
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16 pages, 4726 KiB  
Review
Sirolimus Release from Biodegradable Polymers for Coronary Stent Application: A Review
by Wei Xu, Makoto Sasaki and Takuro Niidome
Pharmaceutics 2022, 14(3), 492; https://doi.org/10.3390/pharmaceutics14030492 - 24 Feb 2022
Cited by 10 | Viewed by 3106
Abstract
Drug-eluting stents (DESs) are commonly used for the treatment of coronary artery disease. The evolution of the drug-eluting layer on the surface of the metal stent plays an important role in DES functionality. Here, the use of biodegradable polymers has emerged as an [...] Read more.
Drug-eluting stents (DESs) are commonly used for the treatment of coronary artery disease. The evolution of the drug-eluting layer on the surface of the metal stent plays an important role in DES functionality. Here, the use of biodegradable polymers has emerged as an attractive strategy because it minimizes the occurrence of late thrombosis after stent implantation. Furthermore, understanding the drug-release behavior of DESs is also important for improving the safety and efficacy of stent treatments. Drug release from biodegradable polymers has attracted extensive research attention because biodegradable polymers with different properties show different drug-release behaviors. Molecular weight, composition, glass transition temperature, crystallinity, and the degradation rate are important properties affecting the behavior of polymers. Sirolimus is a conventional anti-proliferation drug and is the most widely used drug in DESs. Sirolimus-release behavior affects endothelialization and thrombosis formation after DES implantation. In this review, we focus on sirolimus release from biodegradable polymers, including synthetic and natural polymers widely used in the medical field. We hope this review will provide valuable up-to-date information on this subject and contribute to the further development of safe and efficient DESs. Full article
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22 pages, 2980 KiB  
Review
Application and Utility of Liposomal Neuroprotective Agents and Biomimetic Nanoparticles for the Treatment of Ischemic Stroke
by Tatsuya Fukuta, Naoto Oku and Kentaro Kogure
Pharmaceutics 2022, 14(2), 361; https://doi.org/10.3390/pharmaceutics14020361 - 04 Feb 2022
Cited by 16 | Viewed by 3025
Abstract
Ischemic stroke is still one of the leading causes of high mortality and severe disability worldwide. Therapeutic options for ischemic stroke and subsequent cerebral ischemia/reperfusion injury remain limited due to challenges associated with drug permeability through the blood-brain barrier (BBB). Neuroprotectant delivery with [...] Read more.
Ischemic stroke is still one of the leading causes of high mortality and severe disability worldwide. Therapeutic options for ischemic stroke and subsequent cerebral ischemia/reperfusion injury remain limited due to challenges associated with drug permeability through the blood-brain barrier (BBB). Neuroprotectant delivery with nanoparticles, including liposomes, offers a promising solution to address this problem, as BBB disruption following ischemic stroke allows nanoparticles to pass through the intercellular gaps between endothelial cells. To ameliorate ischemic brain damage, a number of nanotherapeutics encapsulating neuroprotective agents, as well as surface-modified nanoparticles with specific ligands targeting the injured brain regions, have been developed. Combination therapy with nanoparticles encapsulating neuroprotectants and tissue plasminogen activator (t-PA), a globally approved thrombolytic agent, has been demonstrated to extend the narrow therapeutic time window of t-PA. In addition, the design of biomimetic drug delivery systems (DDS) employing circulating cells (e.g., leukocytes, platelets) with unique properties has recently been investigated to overcome the injured BBB, utilizing these cells’ inherent capability to penetrate the ischemic brain. Herein, we review recent findings on the application and utility of nanoparticle DDS, particularly liposomes, and various approaches to developing biomimetic DDS functionalized with cellular membranes/membrane proteins for the treatment of ischemic stroke. Full article
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2021

Jump to: 2022

10 pages, 2897 KiB  
Article
Liposomal Artificial Red Blood Cell-Based Carbon Monoxide Donor Is a Potent Renoprotectant against Cisplatin-Induced Acute Kidney Injury
by Kazuaki Taguchi, Yuto Suzuki, Moeko Tsutsuura, Kana Hiraoka, Yuki Watabe, Yuki Enoki, Masaki Otagiri, Hiromi Sakai and Kazuaki Matsumoto
Pharmaceutics 2022, 14(1), 57; https://doi.org/10.3390/pharmaceutics14010057 - 27 Dec 2021
Cited by 5 | Viewed by 2403
Abstract
Cisplatin (CDDP) is an essential anti-tumor agent for chemotherapeutic regimens against various types of cancer. However, the progression of nephrotoxicity, which is the main adverse effect of CDDP, leads to discontinuation of CDDP chemotherapy. Therefore, development of a renoprotectant against CDDP-induced nephrotoxicity is [...] Read more.
Cisplatin (CDDP) is an essential anti-tumor agent for chemotherapeutic regimens against various types of cancer. However, the progression of nephrotoxicity, which is the main adverse effect of CDDP, leads to discontinuation of CDDP chemotherapy. Therefore, development of a renoprotectant against CDDP-induced nephrotoxicity is crucial. Here, the potential of a carbon monoxide (CO)-loaded hemoglobin-vesicle (CO-HbV) as a renoprotectant for CDDP-induced nephrotoxicity was evaluated for its renoprotective effects against CDDP-induced nephrotoxicity, inhibitory effects on the anti-tumor activity of CDDP, and anti-tumor activity. In healthy mice, after pretreatment with either saline, HbV, or CO-HbV prior to CDDP administration, only the CO-HbV pretreatment group ameliorated the progression of CDDP-induced nephrotoxicity by suppressing apoptosis via caspase-3. In experiments using B16-F10 melanoma cells, the half-maximal inhibitory concentration of CDDP decreased with co-incubation with CO-HbV, owing to the anti-tumor activity of CO. CO-HbV pretreatment had no impact on the anti-tumor activity of CDDP in B16-F10 melanoma cell-bearing mice, which was consistent with the results of the cell experiment. Furthermore, CO-HbV pretreatment improved body growth and survival rates. In conclusion, CO-HbV pretreatment is a potent renoprotectant for CDDP-induced nephrotoxicity, allowing treatment with CDDP to be conducted without failure of cancer treatment. Full article
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15 pages, 4794 KiB  
Article
Investigation of the Transport Pathways Associated with Enhanced Brain Delivery of Peptide Drugs by Intranasal Coadministration with Penetratin
by Noriyasu Kamei, Susumu Suwabe, Kenji Arime, Hidemi Bando, Kaho Murata, Maika Yamaguchi, Natsuki Yokoyama, Erina Tanaka, Ayaka Hashimoto, Takanori Kanazawa, Yukio Ago and Mariko Takeda-Morishita
Pharmaceutics 2021, 13(11), 1745; https://doi.org/10.3390/pharmaceutics13111745 - 20 Oct 2021
Cited by 10 | Viewed by 2416
Abstract
We previously found that coadministering peptides and proteins with the cell-penetrating peptide L-penetratin intranasally significantly increased transport to the brain and enhanced pharmacological effects. The present study aimed to clarify the mechanisms of nose-to-brain drug delivery enhancement by L-penetratin coadministration. First, we compared [...] Read more.
We previously found that coadministering peptides and proteins with the cell-penetrating peptide L-penetratin intranasally significantly increased transport to the brain and enhanced pharmacological effects. The present study aimed to clarify the mechanisms of nose-to-brain drug delivery enhancement by L-penetratin coadministration. First, we compared the concentrations of Exendin-4 in plasma and brain after intranasal and subcutaneous administration and suggested that coadministration with L-penetratin facilitated the direct nose-to-brain transport of Exendin-4. Second, we demonstrated that L-penetratin did not stimulate the transport of Cy7-labeled Exendin-4 and insulin through the trigeminal nerves but shifted their distribution to the olfactory mucosal pathway. Third, we investigated the distribution of insulin into the deeper regions of the brain after delivery via the olfactory pathway and suggested that insulin had entered the olfactory bulb, bottom part of the brain, and perivascular space through the cerebrospinal fluid and had diffused throughout the brain. We further demonstrated that intranasally delivered insulin with L-penetratin specifically accumulated on the hippocampus neuronal cells. Thus, this study suggested that administrating peptide drugs intranasally with L-penetratin allows direct transport to the olfactory bulb, bottom part of the brain, and perivascular space of the cerebral artery. This technique also potentially allows targeting of specific brain areas. Full article
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16 pages, 2776 KiB  
Article
Design of a Platelet-Mediated Delivery System for Drug-Incorporated Nanospheres to Enhance Anti-Tumor Therapeutic Effect
by Jun-ichiro Jo, Tsubasa Emi and Yasuhiko Tabata
Pharmaceutics 2021, 13(10), 1724; https://doi.org/10.3390/pharmaceutics13101724 - 18 Oct 2021
Cited by 3 | Viewed by 2304
Abstract
The objective of this study is to construct a platelet-mediated delivery system for drug-incorporated nanospheres. Nanospheres of poly(lactic-co-glycolic acid) (PLGA-NS) with different sizes and surface properties were prepared by changing the preparation parameters, such as the type of polymer surfactant, the concentration of [...] Read more.
The objective of this study is to construct a platelet-mediated delivery system for drug-incorporated nanospheres. Nanospheres of poly(lactic-co-glycolic acid) (PLGA-NS) with different sizes and surface properties were prepared by changing the preparation parameters, such as the type of polymer surfactant, the concentration of polymer surfactant and PLGA, and the stirring rate. When incubated with platelets, PLGA-NS prepared with poly(vinyl alcohol) suppressed the platelet activation. Scanning electron microscopic and flow cytometry examinations revealed that platelets associated with PLGA-NS (platelet hybrids, PH) had a similar appearance and biological properties to those of the original platelets. In addition, the PH with PLGA-NS specifically adhered onto the substrate pre-coated with fibrin to a significantly great extent compared with PLGA-NS alone. When applied in an in vitro model of tumor tissue which was composed of an upper chamber pre-coated with fibrin and a lower chamber culturing tumor cells, the PH with PLGA-NS incorporating an anti-tumor drug were delivered to the tumor cells through the specific adhesion onto the upper chamber and, consequently, drug release from the upper chamber took place, resulting in the growth suppression of tumor cells. It is concluded that the drug delivery system based on PH is promising for tumor treatment. Full article
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11 pages, 1608 KiB  
Article
Optimization of Sentinel Lymph Node Imaging Methodology Using Anionic Liposome and Hyaluronidase
by Yu Sakurai, Miho Suzuoki, Masaki Gomi, Hiroki Tanaka and Hidetaka Akita
Pharmaceutics 2021, 13(9), 1462; https://doi.org/10.3390/pharmaceutics13091462 - 14 Sep 2021
Cited by 7 | Viewed by 1938
Abstract
The sentinel lymph node (SLN) is the first lymph node into which lymphatic fluid from tumor tissues flows. The development of a highly sensitive probe for detecting SLNs is desired for the lymph node dissection through intraoperative biopsy. We have previously shown that [...] Read more.
The sentinel lymph node (SLN) is the first lymph node into which lymphatic fluid from tumor tissues flows. The development of a highly sensitive probe for detecting SLNs is desired for the lymph node dissection through intraoperative biopsy. We have previously shown that anionic liposomes tend to accumulate in lymph nodes and that macrophage uptake of liposomes contributes to their accumulation. In the present study, we found that among anionic lipids, phosphatidylserine (PS)-containing liposomes were substantially taken up by macrophages. We identified a new lipid composition to improve the SNL-selectivity of liposome accumulation based on Design-of-Experiment. The optimized PS-containing particles were more selectively accumulate to SLN lymph nodes than existing imaging agents indocyanine green. These results indicate the effectiveness of PS-containing anionic particles in SLN imaging. Full article
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