Inhalable upper critical solution temperature-type polymer nanoparticles with gradient spatial protonation and...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Respiratory Drug Delivery

Background:

• Inhalable nanodelivery faces challenges with mucus penetration (requires neutral/negative charge) and biofilm disruption (requires positive charge).
• Existing nanocarriers struggle to address these contradictory requirements for effective respiratory treatments.

Purpose of the Study:

• To develop inhalable polymer nanoparticles with dual-responsive properties to overcome physiological barriers.
• To engineer nanoparticles capable of navigating mucus and targeting bacterial biofilms in the respiratory tract.

Main Methods:

• Synthesized poly(acrylamide-co-acrylonitrile) nanoparticles with gradient spatial protonation and thermal expansion.
• Incorporated a triple-level amine system for pH-dependent charge reversal from negative to positive.
• Utilized upper critical solution temperature (UCST) for thermo-responsive antibiotic release.

Main Results:

• Nanoparticles exhibited pH-dependent charge reversal from -13.45 mV (pH 7.4) to +22.51 mV (pH 5.0), facilitating mucus penetration (83%) and biofilm penetration (100%).
• Demonstrated enhanced cellular uptake, efficient lysosomal escape, and inherent antibacterial activity in acidic microenvironments.
• Showcased immunomodulatory effects by promoting anti-inflammatory macrophage polarization.

Conclusions:

• Developed a multifunctional nanocarrier platform overcoming complex biological interfaces for inhalable nanodelivery.
• Gradient spatial protonation and charge reversal offer a promising strategy for smart nanocarrier design.
• These nanoparticles present a viable approach for enhanced respiratory drug delivery and infection treatment.