Frequency of Mechanical Stress Events Governs Ultrasound-Assisted Drug Delivery: A Modified Rayleigh-Plesset Modeling Approach
Affiliation Type:
Academia
Keywords:
Ultrasound-assisted drug delivery, Cavitation, Rayleigh-Plesset Modeling, Mechanical Stress Frequency
Abstract:
This study establishes a physics-based framework to optimize ultrasound-mediated drug delivery for retinoblastoma. We modeled microbubble dynamics using a modified Rayleigh-Plesset equation (Marmottant/Zhou) to capture shell-buckling and damping effects. By defining a 10GPa stress threshold for nanoparticles, we predicted intracellular drug concentrations as a function of stress-event frequency. Results demonstrate that drug internalization is governed by the frequency of discrete stress events rather than average intensity. At maximum intensity, microbubbles expanded 3.7-fold (74 micrometer), and while stress frequency increased 1.58-fold, the intracellular AUC rose 10.37-fold. These findings were validated by FACS analysis, showing 95% delivery coverage and MFI > 600 a.u.—a 100-fold increase over nanoparticle-only groups. This frequency-driven framework provides a precise, quantitative guideline for optimizing safe and effective targeted ultrasound therapies.
