TY - JOUR
T1 - Strategy of drug development based on the bioactive gas-carrying capacity of hemoglobin
AU - Taguchi, Kazuaki
AU - Matsumoto, Kazuaki
AU - Maruyama, Toru
AU - Otagiri, Masaki
N1 - Publisher Copyright:
© 2020 The Pharmaceutical Society of Japan.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Bioactive gas molecules, including oxygen, nitric oxide and carbon monoxide (CO), exhibit a variety of physiological activities, and are associated with the onset and progress of some disorders. These facts have led researchers to the development of bioactive gas donors for the treatment of intractable disorders. Hemoglobin is likely an ideal carrier of bioactive gases, since hemoglobin in red blood cells innately carries oxygen in the form of oxyhemoglobin, nitric oxide in the form of S-nitrosohemoglobin, and CO in the form of carbonylhemoglobin. In this study, we attempted to develop a biomimetic CO delivery system using a preparation of hemoglobin. Our strategy for the preparation of this hemoglobin-based CO carrier involves CO being exogenously bound to red blood cells or hemoglobin-encapsulated liposomes, called hemoglobin-vesicles (HbV), which mimic the structure and function of red blood cells. We accumulated evidence that the CO donors-CO-bound red blood cells and CO-bound HbV-showed therapeutic efficacy against intractable disorders in animal models. Here, we describe the potential of hemoglobin-based CO donors, especially CO-bound red blood cells and CO-bound HbV, for the treatment of certain disorders. Hemoglobin-based strategies for the delivery of other bioactive gases for novel drug development are also discussed.
AB - Bioactive gas molecules, including oxygen, nitric oxide and carbon monoxide (CO), exhibit a variety of physiological activities, and are associated with the onset and progress of some disorders. These facts have led researchers to the development of bioactive gas donors for the treatment of intractable disorders. Hemoglobin is likely an ideal carrier of bioactive gases, since hemoglobin in red blood cells innately carries oxygen in the form of oxyhemoglobin, nitric oxide in the form of S-nitrosohemoglobin, and CO in the form of carbonylhemoglobin. In this study, we attempted to develop a biomimetic CO delivery system using a preparation of hemoglobin. Our strategy for the preparation of this hemoglobin-based CO carrier involves CO being exogenously bound to red blood cells or hemoglobin-encapsulated liposomes, called hemoglobin-vesicles (HbV), which mimic the structure and function of red blood cells. We accumulated evidence that the CO donors-CO-bound red blood cells and CO-bound HbV-showed therapeutic efficacy against intractable disorders in animal models. Here, we describe the potential of hemoglobin-based CO donors, especially CO-bound red blood cells and CO-bound HbV, for the treatment of certain disorders. Hemoglobin-based strategies for the delivery of other bioactive gases for novel drug development are also discussed.
KW - Carbon monoxide
KW - Heme
KW - Hemoglobin
KW - Liposome
KW - Red blood cell
UR - http://www.scopus.com/inward/record.url?scp=85078853405&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85078853405&partnerID=8YFLogxK
U2 - 10.1248/yakushi.19-00187-1
DO - 10.1248/yakushi.19-00187-1
M3 - Review article
C2 - 32009035
AN - SCOPUS:85078853405
VL - 140
SP - 141
EP - 146
JO - Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
JF - Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
SN - 0031-6903
IS - 2
ER -