Pulmonary Administration of Microparticulate Antisense Oligonucleotide (ASO) for the Treatment of Lung Inflammation.

Abstract:

:Targeted delivery to the lung for controlling lung inflammation is an area that we have explored in this study. The purpose was to use microparticles containing an antisense oligonucleotide (ASO) to NF-κB to inhibit the production of proinflammatory cytokines. Microparticles were prepared using the B-290 Buchi Spray Dryer using albumin as the microparticle matrix. Physicochemical characterization of the microparticles showed the size ranged from 2 to 5 μm, the charge was - 38.4 mV, and they had a sustained release profile over 72 h. Uptake of FITC-labeled ASO-loaded microparticles versus FITC-labeled ASO solution by RAW264.7 murine macrophage cells was 5-10-fold higher. After pulmonary delivery of microparticles to Sprague-Dawley rats, the microparticles were uniformly distributed throughout the lung and were retained in the lungs until 48 h. Serum cytokine (TNF-α and IL-1β) levels of rats after induction of lung inflammation by lipopolysaccharide were measured until 72 h. Animals receiving ASO-loaded microparticles were successful in significantly controlling lung inflammation during this period as compared to animals receiving no treatment. This study was successful in proving that microparticulate ASO therapy was capable of controlling lung inflammation.

journal_name

AAPS PharmSciTech

journal_title

AAPS PharmSciTech

authors

Ubale RV,Shastri PN,Oettinger C,D'Souza MJ

doi

10.1208/s12249-018-1002-7

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

1908-1919

issue

4

issn

1530-9932

pii

10.1208/s12249-018-1002-7

journal_volume

19

pub_type

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