Pharmaceutical Research

, Volume 31, Issue 11, pp 3095–3105 | Cite as

Aerosolized Montelukast Polymeric Particles—An Alternative to Oral Montelukast–Alleviate Symptoms of Asthma in a Rodent Model

Research Paper

ABSTRACT

Purpose

Cysteinyl leukotrienes (CysLTs) propagate inflammatory reactions that result from allergen exposure in asthma. Montelukast, a CysLT type-1 receptor antagonist, disrupts mediator–receptor interactions and minimizes inflammatory response. In this study, we have evaluated anti-asthmatic efficacy of inhalable montelukast-loaded large porous particulate formulations in ovalbumin-induced rat airway inflammation model that mimics asthma.

Methods

The anti-inflammatory effects of a montelukast-loaded formulation were investigated in rats by measuring the total protein content, levels of injury markers and number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). The histopathological studies assessed the morphological and structural changes that occur in asthmatic lungs. Animals were also challenged with methacholine to examine the airway hyper-reactivity.

Results

Compared with healthy animals, asthmatic animals showed a 3.8- and 4.77-fold increase in the protein content and number of inflammatory cells in BALF, respectively. Intratracheal montelukast particles reduced the protein content by 3.3-fold and the number of inflammatory cells by 2.62-fold. Also, montelukast particles reduced the lactate dehydrogenase (LDH) and myeloperoxidase (MPO) levels by a 4.87- and 6.8-fold in BALF, respectively. Montelukast particles reduced the airway wall thickness by 2.5-fold compared with untreated asthmatic lungs. Further, particulate formulation protected the lungs against methacholine-induced bronchial provocation (p < 0.05).

Conclusions

Respirable large porous particles containing montelukast alleviated allergen-induced inflammatory response in an animal model and prevented histological changes associated with asthma. Thus montelukast-loaded large porous polylactic acid (PLA) particles could be an aerosolized delivery approach for administration of currently available oral montelukast.

KEY WORDS

anti-inflammatory asthma microparticles montelukast PLA 

ABBREVIATIONS

ANOVA

Analysis of variance

BALF

Bronchoalveolar lavage fluid

CysLT1

Cysteinyl leukotriene type-1 receptor

EF50

Tidal midexpiratory flow

HRP

Horseradish peroxidase

IT

Intratracheal

IV

Intravenous

LDH

Lactate dehydrogenase

MMAD

Mass median aerodynamic diameter

MPO

Myeloperoxidase

NAD

Nicotinamide adenine dinucleotide

OVA

Ovalbumin

PEI

Polyethylenimine

PLA

Poly (lactic acid)

PLGA

Poly (lactide-co- glycolic acid)

SD

Sprague–Dawley

TMBZ

3, 3′-5, 5′-Tetramethylbenzidine

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Brijeshkumar Patel
    • 1
  • Nilesh Gupta
    • 1
  • Fakhrul Ahsan
    • 1
  1. 1.Department of Pharmaceutical Sciences, School of PharmacyTexas Tech University Health Sciences CenterAmarilloUSA

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