자료유형 | 학위논문 |
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서명/저자사항 | Delivering Antibodies to the Brain: Distribution, Transport Mechanisms, and Dose-Response following Intranasal or Systemic Administration. |
개인저자 | Kumar, Niyanta N. |
단체저자명 | The University of Wisconsin - Madison. Pharmaceutical Sciences. |
발행사항 | [S.l.]: The University of Wisconsin - Madison., 2018. |
발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2018. |
형태사항 | 353 p. |
기본자료 저록 | Dissertations Abstracts International 81-02B. Dissertation Abstract International |
ISBN | 9781085559478 |
학위논문주기 | Thesis (Ph.D.)--The University of Wisconsin - Madison, 2018. |
일반주기 |
Source: Dissertations Abstracts International, Volume: 81-02, Section: B.
Advisor: Thorne, Robert G. |
이용제한사항 | This item must not be sold to any third party vendors. |
요약 | This work investigated the potential of intranasal delivery to rapidly and non-invasively target antibodies to the brain. Using complementary fluorescence and radiometric techniques, we demonstrated that full length immunoglobulin G (IgG) antibodies can access extracellular distribution pathways associated with the olfactory and trigeminal nerves to reach the olfactory bulbs and brainstem respectively, and the perivascular space (PVS) associated with cerebral blood vessels to subsequently distribute within the brain parenchyma. We also observed that for IgG doses resulting in similar blood levels following intranasal or intra-arterial delivery, the levels in the brain were significantly higher with intranasal administration. Overall, our findings suggest that intranasal application of IgG can rapidly achieve therapeutically relevant brain concentrations (mid picomolar to low nanomolar range) by accessing pathways that bypass the blood-brain barrier. We also found that protein size and receptor binding may affect the capacity of antibodies to access or exit the PVS. The brain soluble protein fraction following intranasal delivery of radiolabeled IgG yielded distinct heavy and light chain radiolabeled protein bands |
일반주제명 | Pharmaceutical sciences. |
언어 | 영어 |
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