Wenbo Zhan

Purpose and Objectives: Hydrogel-nanocarrier systems have emerged as a clinically implementable strategy to reduce glioblastoma recurrence following surgery. Despite demonstrated feasibility, the influence of intrinsic tissue and nanocarrier properties on delivery outcomes remains insufficiently understood. This study aims to quantify their individual effects on delivery performance. Methods: A mathematical model is applied to simulate hydrogel-mediated nanocarrier delivery to the oedematous postoperative brain. Simulations are conducted in a realistic 3-D brain geometry rebuilt from medical imaging data. Nine factors are investigated, including drug release rate, nanocarrier diffusivity, blood drainage rate, partitioning at the cell membrane and within cells, drug loading dose, oedema severity, blood pressure, and tissue permeability. Results: The modelling reveals distinct responses of delivery outcomes to each factor. Optimal ranges are identified that maximise drug availability and/or improve distribution volume and uniformity. The results suggest that drug delivery is controlled predominantly by drug release and elimination rather than transport. Conclusions: These findings enhance understanding of the coupled interactions between drug transport and brain tissue in the post-operative environment and provide a quantitative reference for the optimisation of hydrogel-nanocarrier delivery systems to improve inhibition of glioblastoma recurrence.

Purpose and objective: Microneedles have emerged as a promising platform for transdermal drug delivery, offering high patient compliance, ease of use, and minimal invasiveness. Despite extensive research on microneedle design and fabrication, the influence of intrinsic drug properties on delivery performance remains insufficiently understood. This study is aimed to determine the individual effects of key transport properties of the loaded drug on delivery outcomes across different skin layers and the systemic circulation. Methods: A multiphysics model is employed to characterise transdermal drug delivery via microneedles, based on a multilayer skin model that incorporates realistic anatomical structures and dimensions. Nine key drug-related parameters are investigated, including drug diffusivity in the microneedle and skin tissues, partition coefficients between the tissue and microneedle, between the cell membrane and interstitial space, and between the cell interior and interstitial space, as well as the protein binding coefficient, transvascular permeability, elimination rate in the skin tissue, and plasma clearance. Results: The simulations reveal distinct responses of drug delivery performance in each skin layer and in the blood circulation to variations in each property, with optimal values existing depending on the location of the therapeutic target within the skin. Conclusions: The findings provide mechanistic insights into the interplay between drug physicochemical characteristics and transdermal transport dynamics, offering valuable guidance for rational drug selection, formulation design, and the development of microneedle-based therapeutics.

Glioblastoma recurrence after surgery is a major contributor to its high mortality, primarily occurring near the original tumour margin. Various hydrogels have been developed to fill the post-surgical cavity and deliver drugs to the surrounding brain tissue to eliminate residual cells. However, the impact of tissue, hydrogel, and drug properties on delivery outcomes remains unclear. Here, a parametric study is conducted to investigate these effects using mathematical modelling. The results show that post-surgical oedema strongly influences delivery: longer duration or delayed onset of oedema can homogenise drug distribution, with delayed onset yielding a larger and more sustained therapeutic drug volume. Hydrogels with higher permeability or lower drug affinity enhance early concentration and distribution but decline faster over time. Drugs with lower intracellular partitioning improve early efficacy, whereas those with stronger binding to cellular or extracellular components sustain delivery longer. Lower transvascular permeability and slower elimination further enhance outcomes, while extracellular diffusivity must be optimised to maximise drug concentration and distribution. These findings provide guidance for optimising hydrogel-based drug delivery systems to prevent glioblastoma recurrence. Graphical abstract

Hypoxia is considered a critical factor in the development of aneurysms, often associated with disturbed blood flow within dilated arteries. This study aims to explore the impact of such disturbed flow on transmural oxygen transport by modelling blood flow and oxygen dynamics within the lumen and across the multi-layered structure of the arterial wall. The findings reveal that wall shear stress, determined by disturbed blood flow, plays a crucial role in shaping oxygen distribution on the endothelium (END). Oxygen concentrations are generally lower in the dilated region, with distribution being highly heterogeneous. Significantly low oxygen values are found at the boundaries of the dilation and possibly at the midpoint. The predicted velocity of transmural interstitial fluid flow is located in the range from 0.01 μ m s − 1 to 0.1 μ m s − 1 . Oxygen primarily relies on diffusion to traverse the arterial wall layers, and its accumulation is affected by multiple factors. The average oxygen concentration in the inner layers of END, intima, and internal elastic lamina decreases as the length of the dilation increases, while a reduction in these concentrations with increasing dilation severity is observed only when the severity exceeds a critical threshold of 50%. In contrast, the average oxygen concentration in the middle layer of media (MED) increases as the aneurysm develops radially and axially, primarily due to a reduction in MED thickness. Moreover, increased blood flow velocity can effectively alleviate hypoxia across all layers of the arterial wall. The oxygen concentration at a single location does not adequately reflect the layer-wide oxygen distribution within the dilated arterial wall. These findings contribute to a deeper understanding of transmural oxygen transport mechanisms and offer insights into the progression of aneurysms.