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

  • Ruhi V. Ubale
  • Prathap Nagaraja Shastri
  • Carl Oettinger
  • Martin J. D’Souza
Research Article

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.

KEY WORDS

microparticles spray drying inflammation antisense oligonucleotide pulmonary delivery 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Ruhi V. Ubale
    • 1
  • Prathap Nagaraja Shastri
    • 1
  • Carl Oettinger
    • 1
  • Martin J. D’Souza
    • 1
  1. 1.Department of Pharmaceutical Sciences, College of PharmacyMercer UniversityAtlantaUSA

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