Numerical and experimental evaluation of ultrasound-assisted convection enhanced delivery to transfer drugs into brain tumors.

Central Nervous System (CNS) malignant tumors are a leading cause of death worldwide with a high mortality rate. While numerous strategies have been proposed to treat CNS tumors, the treatment efficacy is still low mainly due to the existence of the Blood-Brain Barrier (BBB). BBB is a natural cellular layer between the circulatory system and brain extracellular fluid, limiting the transfer of drug particles and confining the routine treatment strategies in which drugs are released in the blood. Consequently, direct drug delivery methods have been devised to bypass the BBB. However, the efficiency of these methods is not enough to treat deep and large brain tumors. In the study at hand, the effect of focused ultrasound (FUS) waves on enhancing drug delivery to brain tumors, through ultrasound-assisted convection-enhanced delivery (UCED), has been investigated. First, brain mimicking gels were synthesized to mimic the CNS microenvironment, and the drug solution was injected into them. Second, FUS waves with the resonance frequency of 1.1 MHz were applied to the drug injected zone. Next, a finite element (FE) model was developed to evaluate the pre-existing equation in the literature for describing the drug delivery via acoustic streaming in brain tissue. Experimental results showed that the FUS transducer was able to enhance the drug volume distribution up to 500% relative to convection-enhanced delivery alone (CED). Numerical analysis showed that the FE model could replicate the experimental penetration depths with a mean difference value of less than 21%, and acoustic streaming plays a significant role in UCED. Therefore, the results of this study could open a new way to develop FE models of the brain to better evaluate the UCED and reduce the costs of conducting clinical and animal studies.

Modeling of an Ultrasound System in Targeted Drug Delivery to Abdominal Aortic Aneurysm: A Patient-Specific in Silico Study Based on Ligand-Receptor Binding.

Targeted drug delivery methods have shown a significant impact on enhancing drug delivery efficiency and reducing drug side effects. While various stimuli have been used to promote the drug delivery process, applying ultrasound (US) waves to control drug particles through the human body, noninvasively, has drawn the scientist's attention. However, microcarriers delivery reaches the aneurysmal artery by US waves that exert volumetric forces on blood, and drug carriers, which can therefore affect blood flow patterns and movement pathways of drug carriers, have not yet been studied. In this study, we developed a 3-D patient-specific model of abdominal aortic aneurysm (AAA) to evaluate the effect of US waves in enhancing the drug-containing microbubbles (MBs) adhered on the AAA lumen through ligand-receptor binding. Thus, a focused US (FUS) transducer with a resonance frequency of ~1.1 MHz was added to the geometry. Then, the surface density of MBs (SDM) adhered on the AAA lumen was calculated at peak acoustic pressure of ~1.1, ~2.2, and ~4.3 MPa. Results indicated that increasing the US pressure had a significant impact on improving the MBs adhered to the intended wall, whereby US waves with the maximum pressure of ~4.3 MPa could enhance ~1- [Formula: see text] MBs adhesion ~98% relative to not using the waves. While US waves have the advantage of more SDM adhered to the whole artery wall, they adversely affect the SDM adhered on the critical wall of the abdominal aorta. Furthermore, when the US strength goes up, a reduction occurs in the SDM adhered. This reduction is higher for smaller MBs, which is the mentioned MBs' size and US strength reduced SDM adhesion by about ~50% relative to systemic injection. Therefore, it can be concluded that drug delivery using the US field increases the SDM adhered to the whole AAA wall and decreases the SDM adhered to the critical wall of AAA.