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020 ▼a 9780438024069
035 ▼a (MiAaPQ)AAI10189859
035 ▼a (MiAaPQ)wisc:13608
040 ▼a MiAaPQ ▼c MiAaPQ ▼d 248032
0820 ▼a 615
1001 ▼a Wolak, Daniel J.
24510 ▼a Distribution of Biologics within the Brain Microenvironment: Focus on Antibodies and Adeno-Associated Viral Vectors.
260 ▼a [S.l.] : ▼b The University of Wisconsin - Madison., ▼c 2016
260 1 ▼a Ann Arbor : ▼b ProQuest Dissertations & Theses, ▼c 2016
300 ▼a 177 p.
500 ▼a Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
500 ▼a Adviser: Robert G. Thorne.
5021 ▼a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2016.
520 ▼a 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
520 ▼a 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
520 ▼a 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
520 ▼a 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
520 ▼a 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
590 ▼a School code: 0262.
650 4 ▼a Pharmaceutical sciences.
650 4 ▼a Neurosciences.
690 ▼a 0572
690 ▼a 0317
71020 ▼a The University of Wisconsin - Madison. ▼b Pharmaceutical Sciences.
7730 ▼t Dissertation Abstracts International ▼g 79-10B(E).
773 ▼t Dissertation Abstract International
790 ▼a 0262
791 ▼a Ph.D.
792 ▼a 2016
793 ▼a English
85640 ▼u http://www.riss.kr/pdu/ddodLink.do?id=T14996502 ▼n KERIS
980 ▼a 201812 ▼f 2019
990 ▼a 관리자