RESUMO
We propose a mathematical model to describe enzyme-based tissue degradation in cancer therapies. The proposed model combines the poroelastic theory of mixtures with the transport of enzymes or drugs in the extracellular space. The effect of the matrix-degrading enzymes on the tissue composition and its mechanical response are accounted for. Numerical simulations in 1D, 2D and axisymmetric (3D) configurations show how an injection of matrix-degrading enzymes alters the porosity of a biological tissue. We eventually exhibit numerically the main consequences of a matrix-degrading enzyme pretreatment in the framework of chemotherapy: the removal of the diffusive hindrance to the penetration of therapeutic molecules in tumors and the reduction of interstitial fluid pressure which improves transcapillary transport. Both effects are consistent with previous biological observations.
Assuntos
Terapia Enzimática , Modelos Biológicos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Algoritmos , Animais , Fenômenos Biomecânicos , Simulação por Computador , Elasticidade , Líquido Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Humanos , Modelos Lineares , Conceitos Matemáticos , Dinâmica não Linear , Porosidade , PressãoRESUMO
BACKGROUND AND OBJECTIVE: The paper focuses on the numerical strategies to optimize a plasmid DNA delivery protocol, which combines hyaluronidase and electroporation. METHODS: A well-defined continuum mechanics model of muscle porosity and advanced numerical optimization strategies have been used, to propose a substantial improvement of a pre-existing experimental protocol of DNA transfer in mice. Our work suggests that a computational model might help in the definition of innovative therapeutic procedures, thanks to the fine tuning of all the involved experimental steps. This approach is particularly interesting in optimizing complex and costly protocols, to make in vivo DNA therapeutic protocols more effective. RESULTS: Our preliminary work suggests that computational model might help in the definition of innovative therapeutic protocol, thanks to the fine tuning of all the involved operations. CONCLUSIONS: This approach is particularly interesting in optimizing complex and costly protocols for which the number of degrees of freedom prevents a experimental test of the possible configuration.