Local controlled drug delivery to the brain: mathematical modeling of the underlying mass transport mechanisms

International Journal of Pharmaceutics
J SiepmannA T Florence

Abstract

The mass transport mechanisms involved in the controlled delivery of drugs to living brain tissue are complex and yet not fully understood. Often the drug is embedded within a polymeric or lipidic matrix, which is directly administered into the brain tissue, that is, intracranially. Different types of systems, including microparticles and disc- or rod-shaped implants are used to control the release rate and, thus, to optimize the drug concentrations at the site of action in the brain over prolonged periods of time. Most of these dosage forms are biodegradable to avoid the need for the removal of empty remnants after drug exhaustion. Various physical and chemical processes are involved in the control of drug release from these systems, including water penetration, drug dissolution, degradation of the matrix and drug diffusion. Once the drug has been released from the delivery system, it has to be transported through the living brain tissue to the target site(s). Again, a variety of phenomena, including diffusion, drug metabolism and degradation, passive or active uptake into CNS tissue and convection can be of importance for the fate of the drug. An overview is given of the current knowledge of the nature of barriers to free acc...Continue Reading

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