Drug & virus transport across biological barriers: interactions, diffusion, partitioning, permeability, and...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pharmacology

Background:

• Biological barriers selectively block foreign materials, impacting drug delivery.
• Mucus barriers in the intestines, lungs, and eyes pose significant challenges for drug administration.
• Current particle design heuristics are limited to diffusion rates within barriers.

Purpose of the Study:

• To develop a cohesive model for particle transport through biological barriers.
• To incorporate partitioning and diffusion contributions for improved transport prediction.
• To establish design rules for drug particles to optimize delivery across mucus.

Main Methods:

• Utilized first-principles theories for colloidal scale interactions.
• Developed analytical models to predict partition coefficients based on particle-pore interaction potentials.
• Incorporated particle-pore hydrodynamics to predict diffusivities within mucus barriers.

Main Results:

• Attractive interactions (specific or non-specific) at the kT-scale optimize the delivery of larger particles.
• Achieved an order of magnitude increase in mass flux across mucus barriers.
• Enabled delivery of macromolecular cargo through enhanced partitioning.

Conclusions:

• Developed a predictive model for particle transport through biological barriers.
• Identified drug particle design rules to enhance transport rates.
• Demonstrated potential for particle transport exceeding that of viruses.