Respirable powder formulation of a shortened vasoactive intestinal peptide analog for treatment of airway inflammatory diseases.
The aim of present study was to develop a respirable powder (RP) of a shortened vasoactive intestinal peptide (VIP) analog for inhalation. VIP and C-terminally truncated VIP analogs were synthesized with a solid-phase method. A structure-activity relationship (SAR) study was carried out in terms with binding and relaxant activities of the peptides. Prepared RP formulation of a shortened VIP analog was physicochemically characterized by morphological, in vitro aerodynamic, and pharmacological assessments. The SAR study demonstrated that the N-terminal 23 amino acid residues were required for biological activity of VIP. Upon chemical modification of VIP(1-23), [R15, 20, 21 , L17 ]-VIP(1-23) was newly developed, which had higher binding activity in rat lung and smooth muscle relaxant effect in mouse stomach than VIP(1-23). The [R15, 20, 21 , L17 ]-VIP(1-23)-based RP, [R15, 20, 21 , L17 ]-VIP(1-23)/RP, exhibited fine in vitro inhalation performance. Airway inflammation evoked by sensitization of antigen in rats was attenuated by pre-treatment with the [R15, 20, 21 , L17 ]-VIP(1-23)/RP at a dose of 50 μg-[R15, 20, 21 , L17 ]-VIP(1-23)/rat as evidenced by a 70% reduction of recruited inflammatory cells in bronchoalveolar lavage fluid. On the basis of these results, [R15, 20, 21 , L17 ]-VIP(1-23)/RP might be a promising agent for treatment of airway inflammatory diseases.
['Suzuki|Hiroki|H|', 'Mizumoto|Takahiro|T|', 'Seto|Yoshiki|Y|http://orcid.org/0000-0002-5976-3630', 'Sato|Hideyuki|H|http://orcid.org/0000-0002-5155-2003', 'Onoue|Satomi|S|']
D000280:Administration, Inhalation D000818:Animals D001249:Asthma D001992:Bronchoalveolar Lavage Fluid D004195:Disease Models, Animal D005765:Gastrointestinal Agents D008168:Lung D008297:Male D051379:Mice D011208:Powders D051381:Rats D013270:Stomach D013329:Structure-Activity Relationship D014660:Vasoactive Intestinal Peptide
respirable powder vasoactive intestinal peptide structure-activity relationship airway inflammation anti-inflammatory effect