Synthetic mucus barrier arrays as a nanoparticle formulation screening platform

Area of Science:

• Biomaterials Science
• Drug Delivery
• Nanotechnology

Background:

• Mucus barriers protect tissues but impede nanoparticle drug delivery.
• Optimizing nanoparticle properties (size, surface chemistry) is crucial for mucus penetration.
• Existing methods for evaluating nanoparticle-mucus interactions are limited.

Purpose of the Study:

• To develop a high-throughput screening platform for evaluating nanoparticle drug delivery through mucus barriers.
• To investigate the impact of nanoparticle design parameters on mucus penetration.
• To assess the efficacy of mucolytic agents as permeation enhancers for mucosal drug delivery.

Main Methods:

• Developed a biomimetic, mucin-based hydrogel to create synthetic mucus barriers.
• Fabricated 3D-printed synthetic mucus barriers compatible with 96-well plates for high-throughput screening.
• Evaluated nanoparticle penetration based on size, polyethylene glycol (PEG) coating, and treatment with tris(2-carboxyethyl) phosphine (TCEP) or N-acetyl cysteine (NAC).

Main Results:

• Smaller nanoparticles and those coated with PEG demonstrated improved penetration through synthetic mucus barriers.
• Tris(2-carboxyethyl) phosphine (TCEP) significantly enhanced nanoparticle penetration compared to N-acetyl cysteine (NAC), especially in disease-mimicking mucus.
• The 96-well plate compatible array enabled efficient screening of nanoparticle formulations.

Conclusions:

• The developed synthetic mucus barrier array provides a robust high-throughput platform for optimizing nanoparticle drug delivery systems.
• Nanoparticle size and surface modification (PEGylation) are key factors for enhancing mucus penetration.
• Tris(2-carboxyethyl) phosphine (TCEP) shows promise as a mucolytic agent to improve drug delivery to mucosal tissues.