Formulation design and in vivo evaluation of dry powder inhalation system of new vasoactive intestinal peptide derivative ([R(15, 20, 21), L(17), A(24,25), des-N(28)]-VIP-GRR) in experimental asthma/COPD model rats.

Abstract

Vasoactive intestinal peptide (VIP) has been considered as a promising drug candidate for asthma and COPD because of its potent immunomodulating and anti-inflammatory activities. Recently, our group developed a new VIP derivative, [R(15, 20, 21), L(17), A(24,25), des-N(28)]-VIP-GRR (IK312548), with improved chemical and metabolic stability. In the present study, a dry powder inhaler system of IK312548 was designed for inhalation therapy with minimal systemic side effects, the physicochemical properties of which were also evaluated with a focus on morphology, particle size distribution, inhalation performance, and peptide stability. Laser diffraction and cascade impactor analysis suggested high dispersion and deposition in the respiratory organs with a fine particle fraction of 31.2%. According to UPLC/ESI-MS and circular dichroic spectral analyses, no significant changes in the purity and structure of VIP derivative were observed during preparation of respirable formulation. Anti-inflammatory properties of IK312548 respirable powder (RP) were characterized in antigen-sensitized asthma/COPD-model rats. There were marked inflammatory cells infiltrated into the lung tissues of experimental asthma/COPD-model rats; however, intratracheal administration of IK312548-RP led to significant reductions of recruited inflammatory cells in lung tissues and BALF by 72 and 78%, respectively. Thus, respirable powder formulation of IK312548 might be a promising medication for asthma, COPD, and other airway inflammatory diseases.

• Authors: Satomi Onoue, Yosuke Aoki, Takuya Matsui, Yoshiki Kojo, Shingen Misaka, Takahiro Mizumoto, Shizuo Yamada
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 410 Issue 1-2 Pg. 54-60 (May 30 2011) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 21419198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• vasoactive intestinal peptide-glycyl-arginyl-arginine, arginyl(15,20,21)-leucyl(17)-alanyl(24,25)-desasparagyl(28)-
• Vasoactive Intestinal Peptide

Topics

• Administration, Inhalation
• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacokinetics, pharmacology)
• Asthma (drug therapy, physiopathology)
• Disease Models, Animal
• Drug Stability
• Dry Powder Inhalers
• Inflammation (drug therapy, physiopathology)
• Lung (drug effects, physiopathology)
• Male
• Particle Size
• Pulmonary Disease, Chronic Obstructive (drug therapy, physiopathology)
• Rats
• Rats, Sprague-Dawley
• Tissue Distribution
• Vasoactive Intestinal Peptide (administration & dosage, analogs & derivatives, pharmacokinetics, pharmacology)