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

Yang, Hong; Cao, Luoxia; Li, Ming; Zhou, Yang

doi:10.1039/d3cp01722b

Cited by 1 publication

(9 citation statements)

References 49 publications

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“…This obviously affects the delivery of therapeutic drugs. Here, we first focused on the delivery of hydrophobic PTX clusters across the BBB and compared them with previous PM results . At a fixed bubble size, the penetration depth of PTX (Δ D PTX ), which was defined as the distance between the initial position of the PTX cluster centroid in the z -direction and the deepest position, satisfies the exponential relationship with the shock wave speed, agreeing with the rule of penetration through the PM .…”

Section: Resultsmentioning

confidence: 70%

“…Thus, the deepest positions we calculated are all in the nonrebound phase. As shown in Figure a, the Δ D PTX across BBB is about 20.6 nm for u p = 0.7 km/s, which is far less than 30.2 nm across PM (about two-thirds) . According to the above analysis, this is obviously related to the unique tight junctions and two-bilayer structure of the BBB.…”

Section: Resultsmentioning

confidence: 85%

“…Here, we first focused on the delivery of hydrophobic PTX clusters across the BBB and compared them with previous PM results. 35 At a fixed bubble size, the penetration depth of PTX (ΔD PTX ), which was defined as the distance between the initial position of the PTX cluster centroid in the z-direction and the deepest position, satisfies the exponential relationship with the shock wave speed, agreeing with the rule of penetration through the PM. 35 The high-speed shock wave will rebound the box boundary within 100 ps, pushing the drugs back to the BBB and affecting the statistical results of ΔD PTX .…”

Section: ■ Results and Discussionmentioning

confidence: 92%

“…At u p = 1.6 km/s, the chain length of siRNA almost increased to 2.6 times compared to the initial structure (from 7 to 18 nm). This change is much greater than when transporting across PM . The characteristic tight junctions and two-bilayer structure in the BBB make it more resistant to shock wave than the PM.…”

Section: Resultsmentioning

confidence: 96%

“…In addition, a cluster of 14 PTXs stay completely in the cytoplasm, and the corresponding absorption rate is about 28%. For cross-PM transport, PTXs with a penetration depth of approximately 20 nm are almost completely absorbed . This is because some dispersed PTXs are located on the side of the BBB deformation area after shock and are easily pulled back into the BBB and embedded in it.…”

Section: Resultsmentioning

confidence: 99%

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Molecular Modeling of Shockwave-Mediated Blood-Brain Barrier Opening for Targeted Drug Delivery

Zhou,

Yang

et al. 2024

ACS Appl. Mater. Interfaces

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Bubble-enhanced shock waves induce the transient opening of the blood-brain barrier (BBB) providing unique advantages for targeted drug delivery of brain tumor therapy, but little is known about the molecular details of this process. Based on our BBB model including 28 000 lipids and 280 tight junction proteins and coarse-grained dynamics simulations, we provided the molecular-level delivery mechanism of three typical drugs for the first time, including the lipophilic paclitaxel, hydrophilic gemcitabine, and siRNA encapsulated in liposome, across the BBB. The results show that the BBB is more difficult to be perforated by shock-induced jets than the human brain plasma membrane (PM), requiring higher shock wave speeds. For the pores formed, the BBB exhibits a greater ability to self-heal than PM. Hydrophobic paclitaxel can cross the BBB and be successfully absorbed, but the amount is only one-third of that of PM; however, the absorption of hydrophilic gemcitabine was almost negligible. Liposome-loaded siRNAs only stayed in the first layer of the BBB. The mechanism analysis shows that increasing the bubble size can promote drug absorption while reducing the risk of higher shock wave overpressure. An exponential function was proposed to describe the relation between bubble and overpressure, which can be extended to the experimental microbubble scale. The calculated overpressure is consistent with the experimental result. These molecular-scale details on shock-assisted BBB opening for targeted drug delivery would guide and assist experimental attempts to promote the application of this strategy in the clinical treatment of brain tumors.

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Section: Resultsmentioning

confidence: 70%

Section: Resultsmentioning

confidence: 85%