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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.

Authors: Onoue, S  Aoki, Y  Matsui, T  Kojo, Y  Misaka, S  Mizumoto, T  Yamada, S 
Citation: Onoue S, etal., Int J Pharm. 2011 May 30;410(1-2):54-60. Epub 2011 Mar 16.
Pubmed: (View Article at PubMed) PMID:21419198
DOI: Full-text: DOI:10.1016/j.ijpharm.2011.03.021

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.


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CRRD Object Information
CRRD ID: 5685381
Created: 2012-01-10
Species: All species
Last Modified: 2012-01-10
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.