University of Kentucky

Poster Title

Dependence of Volume of Distribution on Gel Strength for Convection Enhanced Delivery of Drugs to the Brain

Institution

University of Kentucky

Abstract

Convection Enhanced Delivery (CED) is emerging as an effective clinical method for delivering therapeutic agents directly to the brain to treat neurological diseases, including Parkinson’s disease, which increasingly affects patients from across the world, nation and commonwealth of Kentucky each year. While this method has had varying success in clinical trials, standardized CED in vitro models are needed to develop CED techniques which improve the reliable distribution of therapeutic compounds. Many groups, including ours, have conducted model studies using agarose gel mimics, which simulate the isotropic, porous environment of grey matter structures, such as the putamen. However, the composition of the gels is not defined in the literature. To gain insight into the dependence of the infusion pressure required, and the volume of distribution of compounds as a function of varying agarose gel strength, we infused safranin O dye into 0.6% agarose gels of tensile strengths of 500, 900 and 1200 g/cm3. Our results show that the volume of distribution and the infusion back pressure is dependent on agarose gel strength, with 900 g/cm3 better approximating CED delivery in the porcine brain. This information will be useful for future standardized in vitro evaluations of CED procedures for the improved treatment of neurological disorders.

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Dependence of Volume of Distribution on Gel Strength for Convection Enhanced Delivery of Drugs to the Brain

Convection Enhanced Delivery (CED) is emerging as an effective clinical method for delivering therapeutic agents directly to the brain to treat neurological diseases, including Parkinson’s disease, which increasingly affects patients from across the world, nation and commonwealth of Kentucky each year. While this method has had varying success in clinical trials, standardized CED in vitro models are needed to develop CED techniques which improve the reliable distribution of therapeutic compounds. Many groups, including ours, have conducted model studies using agarose gel mimics, which simulate the isotropic, porous environment of grey matter structures, such as the putamen. However, the composition of the gels is not defined in the literature. To gain insight into the dependence of the infusion pressure required, and the volume of distribution of compounds as a function of varying agarose gel strength, we infused safranin O dye into 0.6% agarose gels of tensile strengths of 500, 900 and 1200 g/cm3. Our results show that the volume of distribution and the infusion back pressure is dependent on agarose gel strength, with 900 g/cm3 better approximating CED delivery in the porcine brain. This information will be useful for future standardized in vitro evaluations of CED procedures for the improved treatment of neurological disorders.