Browsing by Author "Kashaju, Nelson"

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    Modeling the effect of binding kinetics in spatial drug distribution in the brain
    (NM-AIST, 2021-08) Kashaju, Nelson
    Key factors in the process of drug delivery in the human brain are blood-brain barrier, drug dis tribution and drug binding kinetics. Since human brain is entirely unavailable for experimenta tion, mathematical models have become vital for improved visualization of how each of the key factors affects the delivery of drugs in the the human brain. In this study, a 3-dimensional math ematical model that incorporates drug transport across the blood-brain barrier, binding kinetics and drug distribution within the brain extracellular fluid with a bidirectional bulk flow of the brain extracellular fluid was developed and simulated. The model was developed assuming a cube volume of a brain unit that is a union of the blood-brain barrier, brain extracellular fluid and the blood plasma sub-domains. The model includes a set of partial differential equations and boundary conditions that characterize the processes in the specified sub-domains. To determine the effect of drug binding kinetics, the model equations together with their prescribed boundary conditions were discretized by employing the finite difference method implicit schemes and the model was analysed and simulated using MATLAB coding. Effects of drug binding kinetics were investigated by varying the binding parameter values for both specific and non-specific binding sites. All variations of binding parameter values were discussed and the results show the improved visualization of the effect of binding kinetics in drug distribution within the brain. For more realistic visualization, it was suggested to integrate more brain components that make up the large volume of the brain tissue
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    Modeling the Effect of Binding Kinetics in Spatial Drug Distribution in the Brain
    (Hindawi, 2021-07-05) Kashaju, Nelson; Kimathi, Mark; Masanja, Verdiana Grace
    A 3-dimensional mathematical model is developed to determine the effect of drug binding kinetics on the spatial distribution of a drug within the brain. The key components, namely, transport across the blood-brain barrier (BBB), drug distribution in the brain extracellular fluid (ECF), and drug binding kinetics are coupled with the bidirectional bulk flow of the brain ECF to enhance the visualization of drug concentration in the brain. The model is developed based on the cubical volume of a brain unit, which is a union of three subdomains: the brain ECF, the BBB, and the blood plasma. The model is a set of partial differential equations and the associated initial and boundary conditions through which the drug distribution process in the mentioned subdomains is described. Effects of drug binding kinetics are investigated by varying the binding parameter values for both nonspecific and specific binding sites. All variations of binding parameter values are discussed, and the results show the improved visualization of the effect of binding kinetics in the drug distribution within the brain. For more realistic visualization, we suggest incorporating more brain components that make up the large volume of the brain tissue.