Nanosystem drug targeting: Facing up to complex realities

Area of Science:

• Biomedical Engineering
• Materials Science
• Pharmacology

Background:

• Nanoparticle-based drug delivery systems offer potential therapeutic advantages but face significant challenges in vivo.
• Overblown claims for nanoparticle systems often overlook fundamental physical and biological obstacles.
• Understanding these barriers is critical for developing effective drug targeting strategies.

Purpose of the Study:

• To review the obstacles to successful drug targeting and delivery using nanoparticles.
• To critically evaluate the limitations of current nanoparticle and nanosystem-based delivery approaches.
• To identify unmet challenges and propose solutions for quantitative drug delivery.

Main Methods:

• Literature review of physical and biological barriers in drug targeting.
• Analysis of nanoparticle behavior in biological systems (in vivo).
• Discussion of fundamental physics and material science principles relevant to drug delivery.

Main Results:

• Nanoparticles face issues with in vivo instability (flocculation, aggregation).
• Complex hydrodynamics, particle jamming, and heterogeneous tissue access impede delivery.
• Diffusion limitations of both free drugs and nanoparticles in tumor tissues and cells are significant.

Conclusions:

• Fundamental physical laws govern nanoparticle behavior and limit targeting efficacy.
• Quantitative drug delivery to targets like tumors remains a major challenge.
• An international system for standardized in vitro and in vivo testing of nanoparticulate delivery systems is essential for progress.