The Use of Hemoglobin Vesicles for Delivering Medicinal Gas for the Treatment of Intractable Disorders

Taguchi, Kazuaki; Yamasaki, Keishi; Sakai, Hiromi; Maruyama, Toru; Otagiri, Masaki

doi:10.1016/j.xphs.2017.04.006

Cited by 12 publications

(8 citation statements)

References 103 publications

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“…On the other hand, Nagao et al proved that CO-bound hemoglobin-vesicles (CO-HbV), a nanotechnology-based CO donor, could inhibit Nox4-generated ROS generation, and then reduce bleomycin-induced pulmonary fibrosis [41] . Taguchi et al also indicated that HbV possess great potential for retaining CO, which has the cytoprotective effects, such as anti-inflammation and antioxidant [42] . Although the delivery principles and structural of CORM-2 and CO-HbV are different, at least we can prove that CO really has the cytoprotective effects.…”

Section: Discussionmentioning

confidence: 99%

Carbon monoxide releasing molecule-2 attenuates Pseudomonas aeruginosa-induced ROS-dependent ICAM-1 expression in human pulmonary alveolar epithelial cells

Lee¹,

Chiang³

et al. 2018

Redox Biology

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Pseudomonas aeruginosa (P. aeruginosa) infection in the lung is common in patients with cystic fibrosis (CF). Intercellular adhesion molecule-1 (ICAM-1) is known to play a key role in lung inflammation. Acute inflammation and its timely resolution are important to ensure bacterial clearance and limit tissue damage. Carbon monoxide (CO) has been shown to exert anti-inflammatory effects in various tissues and organ systems. Here, we explored the protective effects and mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on P. aeruginosa-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs). We showed that P. aeruginosa induced prostaglandin E2 (PGE2)/interleukin-6 (IL-6)/ICAM-1 expression and monocyte adherence to HPAEpiCs. Moreover, P. aeruginosa-induced inflammatory responses were inhibited by transfection with siRNA of Toll-like receptor 4 (TLR4), PKCα, p47phox, JNK2, p42, p50, or p65. P. aeruginosa also induced PKCα, JNK, ERK1/2, and NF-κB activation. We further demonstrated that P. aeruginosa increased intracellular ROS generation via NADPH oxidase activation. On the other hand, P. aeruginosa-induced inflammation was inhibited by pretreatment with CORM-2. Preincubation with CORM-2 had no effects on TLR4 mRNA levels in response to P. aeruginosa. However, CORM-2 inhibits P. aeruginosa-induced inflammation by decreasing intracellular ROS generation. P. aeruginosa-induced PKCα, JNK, ERK1/2, and NF-κB activation was inhibited by CORM-2. Finally, we showed that P. aeruginosa induced levels of the biomarkers of inflammation in respiratory diseases, which were inhibited by pretreatment with CORM-2. Taken together, these data suggest that CORM-2 inhibits P. aeruginosa-induced PGE2/IL-6/ICAM-1 expression and lung inflammatory responses by reducing the ROS generation and the inflammatory pathways.

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Section: Discussionmentioning

confidence: 99%

Carbon monoxide releasing molecule-2 attenuates Pseudomonas aeruginosa-induced ROS-dependent ICAM-1 expression in human pulmonary alveolar epithelial cells

Lee¹,

Chiang³

et al. 2018

Redox Biology

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“…Since the oxygen delivery capacity of red blood cells can be maintained after the administration of CO-bound Hb-V, this treatment did not induce the deleterious effects of CO. Furthermore, the pharmacokinetic evaluation of CO-bound Hb-V in mice and rats showed that CO was cleared from the blood circulation within 6 h after CO-bound Hb-V administration via exhaled air 26,28) (Fig. 2).…”

Section: Safety and Pharmacokinetic Profiles Of Co-boundmentioning

confidence: 99%

“…2.5.1. Hemorrhagic Shock 28) In rats with hemorrhagic shock, CO-bound Hb-V resuscitation, as well as resuscitation with oxygen-bound Hb-V or red blood cells, resulted in the survival of all rats throughout the observation period (up to 6 h), with immediate recovery of hemodynamic parameters (blood pressure and heart rate) and blood gas parameters (atrial oxygen and carbon dioxide partial pressure, pH, base excess, and lactate). This result indicated that CO-bound Hb-V can serve as a novel resuscitative fluid.…”

Section: Application Of Co-bound Hb-v For the Treatment Of Intractablmentioning

confidence: 99%

“…2.5.2. Lung Fibrosis 30) Since the CO in CO-bound Hb-V is excreted from the lungs, 28) CO-bound Hb-V could be potentially applied for the treatment of respiratory disorders. In a mouse model of lung fibrosis, which was induced by bleomycin, administration of CO-bound Hb-V delayed the progression of lung fibrosis and restored lung function (forced vital capacity).…”

Section: Application Of Co-bound Hb-v For the Treatment Of Intractablmentioning

confidence: 99%

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Pharmaceutical Technology Innovation Strategy Based on the Function of Blood Transport Proteins as DDS Carriers for the Treatment of Intractable Disorders and Cancer

Taguchi

2020

Biological & Pharmaceutical Bulletin

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Blood transport proteins are biogenic molecules with unique and interesting inherent characteristics that make up living organisms. As the utilization of their inherent characteristics can be a groundbreaking strategy to resolve and improve several clinical problems, attempts have been made to develop pharmaceutical and biomedical preparations based on blood transport proteins for the treatment and diagnosis of disorders. Among various blood transport proteins, we focus on the immense potential of hemoglobin and albumin to serve as carriers of biomedical gases (oxygen and carbon monoxide) and anticancer agents (lowmolecular compounds and antisense oligodeoxynucleotides), respectively, for the development of innovative drug delivery systems (DDS) to treat intractable disorders and solid cancers. In this review, I introduce the pharmaceutical technology, strategies, and application of DDS carriers that have been designed on the basis of the structure and function of hemoglobin and albumin. In addition, the prospect of using hemoglobin and albumin as materials for DDS carriers is discussed.

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“…Furthermore, the phospholipid bilayer membrane that consists of a lipid membrane of HbV allows CO to penetrate, and then easily and stably bind to Hb in the form of HbV as well as RBC (Sakai et al., 2008a , b ). Taking advantage of these favorable characteristics of HbV as a CO carrier, we previously developed CO-bound hemoglobin vesicles (CO-HbV) as a new type of CO donor (Taguchi et al., 2017b ). In addition, we also found that a CO-HbV treatment suppressed the onset and progression of intractable inflammatory disorders in a mouse model via anti-inflammatory effects caused by either a decrease in the production of pro-inflammatory cytokines or an increase in the production of anti-inflammatory cytokine (Nagao et al., 2014 , 2016a , 2016b ).…”

Section: Introductionmentioning

confidence: 99%

Biomimetic carbon monoxide delivery based on hemoglobin vesicles ameliorates acute pancreatitis in mice via the regulation of macrophage and neutrophil activity

et al. 2018

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Macrophages play a central role in various inflammatory disorders and are broadly divided into two subpopulations, M1 and M2 macrophage. In the healing process in acute inflammatory disorders, shifting the production of M1 macrophages to M2 macrophages is desirable, because M1 macrophages secrete pro-inflammatory cytokines, whilst the M2 variety secrete anti-inflammatory cytokines. Previous findings indicate that when macrophages are treated with carbon monoxide (CO), the secretion of anti-inflammatory cytokine is increased and the expression of pro-inflammatory cytokines is inhibited, indicating that CO may have a potential to modulate the production of macrophages toward the M2-like phenotype. In this study, we examined the issue of whether CO targeting macrophages using a nanotechnology-based CO donor, namely CO-bound hemoglobin vesicles (CO-HbV), modulates their polarization and show therapeutic effects against inflammatory disorders. The results showed that the CO-HbV treatment polarized a macrophage cell line toward an M2-like phenotype. Furthermore, in an in vivo study using acute pancreatitis model mice as a model of an inflammatory disease, a CO-HbV treatment also tended to polarize macrophages toward an M2-like phenotype and inhibited neutrophil infiltration in the pancreas, resulting in a significant inflammation. In addition to the suppression of acute pancreatitis, CO-HbV diminished a subsequent pancreatitis-associated acute lung injury. This could be due to the inhibition of the systemic inflammation, neutrophil infiltration in the lungs and the production of HMGB-1. These findings suggest that CO-HbV exerts superior anti-inflammatory effects against inflammatory disorders via the regulation of macrophage and neutrophil activity.

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The Use of Hemoglobin Vesicles for Delivering Medicinal Gas for the Treatment of Intractable Disorders

Cited by 12 publications

References 103 publications

Carbon monoxide releasing molecule-2 attenuates Pseudomonas aeruginosa-induced ROS-dependent ICAM-1 expression in human pulmonary alveolar epithelial cells

Carbon monoxide releasing molecule-2 attenuates Pseudomonas aeruginosa-induced ROS-dependent ICAM-1 expression in human pulmonary alveolar epithelial cells

Pharmaceutical Technology Innovation Strategy Based on the Function of Blood Transport Proteins as DDS Carriers for the Treatment of Intractable Disorders and Cancer

Biomimetic carbon monoxide delivery based on hemoglobin vesicles ameliorates acute pancreatitis in mice via the regulation of macrophage and neutrophil activity

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