Experimental studies on squeezing interstitial fluid via transfer of ultrasound momentum (SIF-TUM) in <i>ex vivo</i> chicken and porcine tissues

The ultrasound-assisted transport of drugs or fluorophore-loaded nanoagents plays an important role in the desirable drug delivery and imaging contrasts. Unlike conventional ultrasound techniques that rely on thermal or cavitation effects, this study aims to conduct an experimental investigation into the dynamics of interstitial fluid streaming and tissue recovery in <i>ex vivo</i> chicken breast and porcine loin muscle tissues during and after ultrasound exposures, which has not been experimentally investigated in the literature. Biological tissues consist of both a fluid and a solid matrix, and an ultrasound beam compresses the tissues within a small focal volume from all directions, which generates macroscopic streaming of interstitial fluid and compression of the tissue's solid matrix. After the ultrasonic exposure, the solid matrix undergoes recovery, leading to a backflow of the fluid matrix. Temperature-insensitive sulforhodamine-101 encapsulated poly(lactic-co-glycolic acid) nanoparticles with an average diameter size of 175 nm were locally injected into <i>ex vivo</i> chicken breast and porcine loin muscle tissues to study the ultrasound-induced dynamics in the tissues during and after ultrasound exposure by analyzing the distribution of fluorescence. The changes in fluorescence over time caused by the streaming and backflow of interstitial fluid were studied with two <i>ex vivo</i> tissue models, and a faster recovery was observed in porcine tissues compared with chicken tissues. The ultrasound-induced transportability of the nanoagent in porcine muscle tissues was much higher (∼8.75 times) than in chicken breast tissue likely due to structural differences. The study reveals a promising, non-invasive strategy for enhancing drug delivery in dense tissues by leveraging mechanical ultrasound effects, potentially advancing therapeutic and diagnostic applications.