Numerical study of doxorubicin transdermal delivery for breast cancer treatment using microneedles.

The lack of in vivo studies on the delivery of doxorubicin within human skin, especially the absence of data on the doxorubicin diffusion coefficient, has made understanding its transdermal delivery kinetics challenging. In this study, as a first step, governing equations and finite element methods were employed to reproduce Franz diffusion cell experiment in human cadaver skin. The application of this experiment representative model with a fitting method resulted in approximate values for the diffusivity of doxorubicin across various skin layers. The estimated values were used later to conduct a comprehensive examination of doxorubicin administration for breast tumor treatments. In a 2D axisymmetric model using Fick's Law and then a microneedles array 3D model, crucial parameters effects on delivery efficiency were examined, such as the microneedle tip diameter, tip-to-tip distance, and tumor depth. As highlighted by the findings of this study, these parameters have an impact on the effectiveness of doxorubicin delivery for treating breast tumors. The focus of this research is on the potential of numerical methods in biomedical engineering, which addresses the urgent need for data on doxorubicin diffusion in human skin and offers valuable insights into optimizing drug delivery strategies for enhanced therapeutic outcomes.

Calibration of Drucker-Prager Cap Constitutive Model for Ceramic Powder Compaction through Inverse Analysis.

Phenomenological plasticity models that relate relative density to plastic strain are frequently used to simulate ceramic powder compaction. With respect to the form implemented in finite element codes, they need to be modified in order to define governing parameters as functions of relative densities. Such a modification increases the number of constitutive parameters and makes their calibration a demanding task that involves a large number of experiments. The novel calibration procedure investigated in this paper is based on inverse analysis methodology, centered on the minimization of a discrepancy function that quantifies the difference between experimentally measured and numerically computed quantities. In order to capture the influence of sought parameters on measured quantities, three different geometries of die and punches are proposed, resulting from a sensitivity analysis performed using numerical simulations of the test. The formulated calibration protocol requires only data that can be collected during the compaction test and, thus, involves a relatively smaller number of experiments. The developed procedure is tested on an alumina powder mixture, used for refractory products, by making a reference to the modified Drucker-Prager Cap model. The assessed parameters are compared to reference values, obtained through more laborious destructive tests performed on green bodies, and are further used to simulate the compaction test with arbitrary geometries. Both comparisons evidenced excellent agreement.