Poloxamer-Decorated Polymer Nanoparticles for Lung Surfactant Compatibility

Area of Science:

• Nanomedicine
• Pulmonary Drug Delivery
• Biophysics

Background:

• Polymer nanoparticles delivered to the lungs can disrupt the lung surfactant system.
• Lung surfactant is essential for maintaining the biophysical function of the deep lungs.

Purpose of the Study:

• To investigate if poloxamer surface modification can prevent polymer nanoparticles from interfering with lung surfactant function.
• To determine the optimal poloxamer characteristics for minimizing adverse effects on lung surfactant.

Main Methods:

• Steric shielding of poly(styrene) and poly(lactide) nanoparticles with various poloxamers.
• Assessing the impact of nanoparticle surface coating (thickness, conformation, chain-to-chain distance) on lung surfactant activity (Alveofact) and protein content.
• Evaluating specific poloxamer formulations (188, 338, 407) for their ability to preserve surfactant microstructure and surface activity.

Main Results:

• Poloxamer coating effectively minimized nanoparticle-induced inhibition of lung surfactant.
• Adsorbed layer thickness (>3 nm) and specific poloxamer conformations (e.g., brush-like PEG) were key to preventing adverse effects.
• Poloxamer 188, 338, and 407 formulations successfully avoided perturbation of Alveofact microstructure, surface activity, and surfactant protein content.

Conclusions:

• Poloxamer-modified polymer nanoparticles are a promising platform for respiratory delivery.
• These modified nanoparticles exhibit negligible effects on the biophysical functionality of the lung's lining layer.
• Surface engineering with poloxamers is a viable strategy to ensure the safety of inhaled nanomedicines.