Penetrating the Brain (For Better or For Worse): Biodistribution and Health Considerations of Orally-Delivered Polystyrene Microspheres

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Title
Penetrating the Brain (For Better or For Worse): Biodistribution and Health Considerations of Orally-Delivered Polystyrene Microspheres
Contributors
Makani, Rahim (creator)
Mathiowitz, Edith (Advisor)
Brown University. Department of Molecular Pharmacology, Physiology and Biotechnology (sponsor)
Doi
10.26300/tw73-j727
Copyright Date
2017
Abstract
The brain is a highly-privileged organ within the body. Evolution has ensured that access to brain tissue is tightly regulated against or completely impenetrable to systemically circulating hormones, large molecules, exogenous chemicals and other harmful agents that could pose serious dangers to optimal synaptic and neuronal functioning. This precise control of the brain’s microenvironment is accomplished by the presence of specialized endothelial cells at the level of cerebral capillaries which form the blood-brain barrier. With respect to treating brain disorders and diseases, the blood-brain barrier poses a serious obstacle for delivering medicines, and it is even referred to as a “bottleneck” in drug development and the single most important factor limiting the future growth of neurotherapeutics. The aims for this study are (a) to establish an effective visualization methodology and experimental protocol for investigating novel drug delivery platforms which target the brain, and (b) to examine the potential health concerns, especially at the blood-brain interface, of ingesting polystyrene microspheres which are already ubiquitous in their use in food additives, packaging, cosmetics and other commercial applications. These aims are addressed across two phases in the current investigation. Phase I is a pilot study which seeks to visualize the bio-distribution of unfunctionalized, curcumin-loaded polystyrene (PS-Curcumin) microspheres in brain tissue. The microspheres used in Phase I are delivered only by oral gavage to experimental rats. Phase II seeks to visualize the distribution of unfunctionalized, fluorescent polystyrene (PS) microspheres in brain tissue. The microspheres used in Phase II are delivered across 3 conditions: IV, oral, subcutaneous. Both Phase I and Phase II employ the rat animal model.
Keywords
Biotechnology
Blood-brain barrier
Neurosciences
Drug delivery systems
Polymeric nanoparticles
Confocal microscopy
Nanostructured materials
Nanomedicine
Microspheres
Notes
Thesis (Sc. M.)--Brown University, 2017
Extent
xiv, 74 p.

Citation

Makani, Rahim, "Penetrating the Brain (For Better or For Worse): Biodistribution and Health Considerations of Orally-Delivered Polystyrene Microspheres" (2017). Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/tw73-j727

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