Zwitterionic Inhaler with Synergistic Therapeutics for Reprogramming of M2 Macrophage to Pro-Inflammatory Phenotype

Area of Science:

• Biomedical Engineering
• Pulmonary Medicine
• Nanotechnology

Background:

• Lung diseases are life-threatening, with macrophages playing a critical role in their progression.
• Over-polarized macrophages can exacerbate lung conditions, necessitating methods to modulate their phenotype.
• Pulmonary drug delivery systems (PDS) offer efficient lung targeting but face challenges due to the lung's defense mechanisms.

Purpose of the Study:

• To develop advanced inhalable microparticles for enhanced pulmonary drug delivery.
• To overcome the limitations of conventional PDS, such as mucus adhesion and macrophage evasion.
• To investigate the potential of zwitterion-functionalized microparticles for modulating macrophage phenotypes in lung diseases.

Main Methods:

• Synthesis of zwitterion-functionalized poly(lactide-co-glycolide) (PLGA) inhalable microparticles (ZwPG).
• Evaluation of ZwPG's properties, including nebulizing stability, anti-mucus adhesion, and macrophage evasion.
• Treatment of over-polarized M2 macrophages with ZwPG loaded with dexamethasone (Dex) and pirfenidone (Pir).

Main Results:

• ZwPG demonstrated high nebulizing stability and effective mucus penetration.
• The zwitterion coating facilitated evasion of airway macrophages, enhancing payload delivery.
• Combined Dex/Pir treatment via ZwPG synergistically reprogrammed M2 macrophages towards pro-inflammatory phenotypes.

Conclusions:

• Zwitterion-functionalized PLGA microparticles represent a promising strategy to enhance pulmonary drug delivery efficiency.
• This novel PDS effectively overcomes lung defense barriers, improving therapeutic agent delivery.
• The developed system shows potential for treating lung diseases by reprogramming macrophage polarization.