Bioactive analogues and drug delivery systems of vasoactive intestinal peptide (VIP) for the treatment of asthma/COPD.
Vasoactive intestinal peptide (VIP) is one of the major peptide transmitters in the central and peripheral nervous systems, being involved in a wide range of biological functions. In an airway system where VIP-immunoreactive nerve fibers are present, VIP acts as neurotransmitter or neuromodulator of the inhibitory non-adrenergic and non-cholinergic airway nervous system and influences many aspects of pulmonary biology. A clinical application of VIP has been believed to offer potential benefits in the treatment of chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), however, its clinical application has been limited in the past for a number of reasons, including its extremely short plasma half-life after intravenous administration and difficulty in administration routes. The development of long-acting VIP analogues, in combination with appropriate drug delivery systems, may provide clinically useful agents for the treatment of asthma/COPD. In this review, development of efficacious VIP derivatives, drug delivery systems designed for VIPs and the potential application for asthma/COPD are discussed. We also include original data from our chemical modification experiments and formulation studies, which led to successful development of [R(15, 20, 21), L(17)]-VIP-GRR (IK312532), a potent VIP analogue, and a VIPs-based dry powder inhaler system.
Onoue
Satomi
S
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274-8510, Japan. onoue@fureai.or.jp
Yamada
Shizuo
S
Yajima
Takehiko
T
D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D001667:Binding, Competitive; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000819:agonists / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use*
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide