1.D.234. The Shockwave-mediated Delivery of Paclitaxel Aggregates (SD-PA) Family
Shock-assisted paclitaxel (PTX) transport across the blood-brain barrier (BBB) offers a promising treatment strategy for brain tumors. Based on a realistically complex human brain plasma membrane (PM) model, Mi et al. 2023 investigated the dynamic transmembrane behavior of a PTX cluster by shock induced bubble collapse, focusing on the effect of impulse (I), bubble diameter (D) and arrays. All three factors can control the transport depth (DeltaD(PM)) of PTX. For a fixed D, the DeltaD(PM) grows exponentially with I, DeltaD(PM) approximately exp (I), and eventually reaches a critical depth. But the depth, DeltaD(PM), can be adjusted linearly in a wider range of D. This mainly depends on the size of jets from bubble collapse. For bubble arrays, the bubbles in series can transport PTX deeper than a single bubble, while the parallel does the opposite. In addition, only PTX clusters in the range of jet action can be successfully transported. The absorption of PTX clusters was examined via recovery simulation. Not all PTX clusters across the membrane can be effectively absorbed by cells. The shallow PTX clusters are quickly attracted by the membrane and embedded into it. The critical depth at which PTX clusters can be effectively absorbed is about 20 nm. These molecular-level mechanisms and dynamic processes of PTX clusters crossing the PM may be helpful in optimizing the application of shock-induced bubble collapse for the delivery of PTX to tumor cells (Mi et al. 2023).