자료유형 | 학위논문 |
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서명/저자사항 | Distribution of Biologics within the Brain Microenvironment: Focus on Antibodies and Adeno-Associated Viral Vectors. |
개인저자 | Wolak, Daniel J. |
단체저자명 | The University of Wisconsin - Madison. Pharmaceutical Sciences. |
발행사항 | [S.l.]: The University of Wisconsin - Madison., 2016. |
발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2016. |
형태사항 | 177 p. |
기본자료 저록 | Dissertation Abstracts International 79-10B(E). Dissertation Abstract International |
ISBN | 9780438024069 |
학위논문주기 | Thesis (Ph.D.)--The University of Wisconsin - Madison, 2016. |
일반주기 |
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Adviser: Robert G. Thorne. |
요약 | This 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 |
요약 | The 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 |
요약 | We 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 |
요약 | Finally, 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 |
요약 | The 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 |
일반주제명 | Pharmaceutical sciences. Neurosciences. |
언어 | 영어 |
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