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In this paper, a new higher-order shear and normal deformation theory for the bending and free vibration analysis of sandwich plates with functionally graded isotropic face sheets is developed. The number of unknown functions involved in the present theory is only five, as against six or more in case of other shear and normal deformation theories. The theory accounts for hyperbolic distribution of the transverse shear strains and satisfies the zero traction boundary conditions on the surfaces of the plate without using shear correction factor. The boundary conditions for the plate are assumed to be simply supported in all edges and in the static analysis, the plate is assumed to be subjected to a sinusoidally distributed load. Both symmetric and non-symmetric sandwich plates are considered. The equations of motion are obtained using Hamilton’s principle. Numerical results of present theory are compared with three-dimensional elasticity solutions and other higher-order theories reported in the literature. It can be concluded that the proposed theory is accurate and efficient in predicting the bending and free vibration responses of sandwich plates with functionally graded isotropic face sheets.

It has been hypothesized that continuously releasing drug molecules into the tumor over an extended period of time may significantly improve the chemotherapeutic efficacy by overcoming physical transport limitations of conventional bolus drug treatment. In this paper, we present a generalized space- and time-dependent mathematical model of drug transport and drug-cell interactions to quantitatively formulate this hypothesis. Model parameters describe: perfusion and tissue architecture (blood volume fraction and blood vessel radius); diffusion penetration distance of drug (i.e., a function of tissue compactness and drug uptake rates by tumor cells); and cell death rates (as function of history of drug uptake). We performed preliminary testing and validation of the mathematical model using in vivo experiments with different drug delivery methods on a breast cancer mouse model. Experimental data demonstrated a 3-fold increase in response using nano-vectored drug vs. free drug delivery, in excellent quantitative agreement with the model predictions. Our model results implicate that therapeutically targeting blood volume fraction, e.g., through vascular normalization, would achieve a better outcome due to enhanced drug delivery.Author SummaryCancer treatment efficacy can be significantly enhanced through the elution of drug from nano-carriers that can temporarily stay in the tumor vasculature. Here we present a relatively simple yet powerful mathematical model that accounts for both spatial and temporal heterogeneities of drug dosing to help explain, examine, and prove this concept. We find that the delivery of systemic chemotherapy through a certain form of nano-carriers would have enhanced tumor kill by a factor of 2 to 4 over the standard therapy that the patients actually received. We also find that targeting blood volume fraction (a parameter of the model) through vascular normalization can achieve more effective drug delivery and tumor kill. More importantly, this model only requires a limited number of parameters which can all be readily assessed from standard clinical diagnostic measurements (e.g., histopathology and CT). This addresses an important challenge in current translational research and justifies further development of the model towards clinical translation.

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