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

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Lung inflammation involves complex pathways, including the NF-κB signaling cascade.
• Targeted delivery of therapeutic agents to the lungs remains a challenge.
• Antisense oligonucleotides (ASO) offer a promising strategy for gene silencing and controlling inflammation.

Purpose of the Study:

• To develop and evaluate microparticles loaded with an antisense oligonucleotide (ASO) targeting NF-κB for controlling lung inflammation.
• To assess the physicochemical properties, cellular uptake, and in vivo biodistribution of ASO-loaded microparticles.
• To determine the efficacy of microparticulate ASO therapy in reducing proinflammatory cytokines and controlling lung inflammation.

Main Methods:

• Microparticles were fabricated using albumin as a matrix via spray drying.
• Physicochemical characterization included size, charge, and drug release studies.
• Cellular uptake was assessed in RAW264.7 macrophage cells, and in vivo studies were conducted in Sprague-Dawley rats with lipopolysaccharide-induced lung inflammation.

Main Results:

• Microparticles exhibited a size range of 2-5 μm, a negative charge (-38.4 mV), and sustained release over 72 hours.
• ASO-loaded microparticles showed 5-10 fold higher uptake by macrophages compared to ASO solution.
• Pulmonary delivery resulted in uniform lung distribution and retention up to 48 hours, with significant reduction in serum TNF-α and IL-1β levels.

Conclusions:

• Microparticulate ASO delivery is an effective strategy for targeted lung delivery and controlling lung inflammation.
• The developed microparticles demonstrate favorable physicochemical properties and enhanced cellular uptake.
• This approach holds significant potential for the therapeutic management of inflammatory lung diseases.