Focal opening of the neuronal plasma membrane by shock-induced bubble collapse for drug delivery: a coarse-grained molecular dynamics simulation

Abstract

Cell permeabilization using shock-induced bubble collapse provides an attractive choice of drug delivery system. In this work, based on a realistically human brain plasma membrane (PM) model, we investigated the...

Molecular modelling of shockwave-mediated delivery of paclitaxel aggregates across the neuronal plasma membrane

“…With the increase of the bubble size, the hemispherical deformation region of the PM membrane has a large convex radius along the z -axis, which is very consistent with the result of pure jet action. 28,44 In detail, the PTX cluster embedded in the PM moved with the deformation progress of the membrane, as shown in Fig. 5.…”

“…As for the effect of bubbles on I , there have been explanations. 28 In this way, we have determined the influence of impulse and bubble size on the PTX transport depth, both of which can be controlled by experimental or clinical equipment. For instance, the impulse can be adjusted by the laser beam fluence of shock wave sources, and the bubble sizes are also easily obtained by centrifugation or using different types of ultrasound contrast agents.…”

“…The maximum area data of these openings are basically the same as the previous results. 28,33 In the parallel alignment, the area sum of two pores is about 127 nm 2 , only 1.6 times that of the single bubble. Thus, we can qualitatively judge that if the jets from the two-bubble arrays can act on the PTX cluster, the order of transport Δ D PM should be as follows, model 9 > model 6 (or 7) > model 2 > model 8.…”

“…For such pore, we have previously performed longer recovery where the pore continues to shrink, but complete healing has not been observed in the limited simulation time. 28,47 Importantly, the dispersed PTX (several small clusters) was completely out of the control of the membrane, although there is a small amount of dispersed lipids around them. Although the PTX moved closer to the membrane, we can still infer that the PTX (including those diffused lipids) would not return to the PM until the membrane is completely recovered.…”

“…Since the PM model was well equilibrated in the previous work, 27 the membrane/water system in this step only needs to balance the water. A similar model has been used to explore the opening of shock wave induced bubble collapse, 28 so the parameter details will not be repeated here. Secondly, in order to obtain a PTX cluster, we placed 125 PTX molecules into a cube simulation box of 30 × 30 × 30 nm 3 with more than 2 × 10 5 ample water molecules, which quickly aggregated into several clusters due to the strong lipophilicity through a 1 μs MD simulation.…”