Microcapsule drug delivery device for treatment of glioblastoma multiforme

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2010.

Bibliographic Details
Main Author: Scott, Alexander Wesley
Other Authors: Michael J. Cima and Robert S. Langer.
Format: Thesis
Language:eng
Published: Massachusetts Institute of Technology 2010
Subjects:
Online Access:http://hdl.handle.net/1721.1/59246
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author Scott, Alexander Wesley
author2 Michael J. Cima and Robert S. Langer.
author_facet Michael J. Cima and Robert S. Langer.
Scott, Alexander Wesley
author_sort Scott, Alexander Wesley
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description Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2010.
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spelling mit-1721.1/592462019-04-10T15:40:26Z Microcapsule drug delivery device for treatment of glioblastoma multiforme Scott, Alexander Wesley Michael J. Cima and Robert S. Langer. Massachusetts Institute of Technology. Dept. of Materials Science and Engineering. Massachusetts Institute of Technology. Dept. of Materials Science and Engineering. Materials Science and Engineering. Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2010. Includes bibliographical references (p. 87-93). Controlled-release drug delivery systems are capable of treating debilitating diseases, including cancer. Brain cancer, in particular glioblastoma multiforme (GBM), is an extremely invasive cancer with a dismal prognosis. The use of drugs capable of crossing the blood-brain barrier has shown modest prolongation in patient survival, but not without unsatisfactory systemic, dose-limiting toxicity. Localized delivery of potent chemotherapeutics aims to lower systemic toxicity while increasing drug concentrations directly to the tumor site. I have developed implantable drug delivery microcapsule devices for the localized delivery of temozolomide and for treatment of glioblastoma multiforme in this work. I have been able to modulate the drug release profiles from these microcapsules based on the physical chemistry of the drug and the dimensions of the release orifices in these devices. Experimental in vitro studies were performed in order to test the function, reliability, and drug release kinetics of the devices. The experimental release curves showed mass flow rates of 36 ug/hr for single-orifice devices and an 88 ug/hr mass flow rate for multiple-orifice devices loaded with temozolomide. Intracranial temozolomide-filled microcapsules were tested in a rodent 9L glioma model. Outcomes were animal survival and immunohistochemical analysis of tissue for evidence of DNA strand breaks via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results showed that localized delivery of chemotherapeutics from microcapsule devices is capable of prolonging animal survival and may offer an alternative to the harsh side-effects and low response rates inherent to systemic drug administration in GBM patients. by Alexander Wesley Scott. S.M. 2010-10-12T18:55:27Z 2010-10-12T18:55:27Z 2010 2010 Thesis http://hdl.handle.net/1721.1/59246 666855731 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 93 p. application/pdf Massachusetts Institute of Technology
spellingShingle Materials Science and Engineering.
Scott, Alexander Wesley
Microcapsule drug delivery device for treatment of glioblastoma multiforme
title Microcapsule drug delivery device for treatment of glioblastoma multiforme
title_full Microcapsule drug delivery device for treatment of glioblastoma multiforme
title_fullStr Microcapsule drug delivery device for treatment of glioblastoma multiforme
title_full_unstemmed Microcapsule drug delivery device for treatment of glioblastoma multiforme
title_short Microcapsule drug delivery device for treatment of glioblastoma multiforme
title_sort microcapsule drug delivery device for treatment of glioblastoma multiforme
topic Materials Science and Engineering.
url http://hdl.handle.net/1721.1/59246
work_keys_str_mv AT scottalexanderwesley microcapsuledrugdeliverydevicefortreatmentofglioblastomamultiforme