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Distribution of Biologics within the Brain Microenvironment: Focus on Antibodies and Adeno-Associated Viral Vectors

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서명/저자사항Distribution of Biologics within the Brain Microenvironment: Focus on Antibodies and Adeno-Associated Viral Vectors.
개인저자Wolak, Daniel J.
단체저자명The University of Wisconsin - Madison. Pharmaceutical Sciences.
발행사항[S.l.]: The University of Wisconsin - Madison., 2016.
발행사항Ann Arbor: ProQuest Dissertations & Theses, 2016.
형태사항177 p.
기본자료 저록Dissertation Abstracts International 79-10B(E).
Dissertation Abstract International
ISBN9780438024069
학위논문주기Thesis (Ph.D.)--The University of Wisconsin - Madison, 2016.
일반주기 Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Adviser: Robert G. Thorne.
요약This dissertation investigated the diffusion and distribution of antibody-based therapeutics and viral vectors within the brain extracellular space. We hypothesized that for these large biologics diffusion in brain is more hindered relative to f
요약The diffusion properties of full-length immunoglobulin G (IgG) were determined in free solution and in the cortex of anesthetized rats. The effective diffusion coefficient (D*) of IgG in rat somatosensory cortex was ~10-fold lower than the free
요약We further examined methods to improve antibody-based therapeutic distribution in brain utilizing smaller antibody fragments and osmotic manipulation of the brain microenvironment. The diffusion of antibody fragments like bivalent antigen-bindin
요약Finally, the diffusion properties of adeno-associated viral (AAV) vectors were explored. The diffusion of AAV8 was significantly hindered in brain compared to free medium (D* was 20-fold lower than D). While D* of AAV2 was not directly measured
요약The results presented in this thesis demonstrate that diffusion measurements of biologics in the brain can be used to illustrate important factors involved in local therapeutic distribution, to develop models to predict penetration into the brai
일반주제명Pharmaceutical sciences.
Neurosciences.
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