Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain
Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood–brain barrier. Efforts at delivering chemotherapy locally to gl...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
National Academy of Sciences (U.S.)
2015
|
| Online Access: | http://hdl.handle.net/1721.1/96952 https://orcid.org/0000-0003-2379-6139 https://orcid.org/0000-0002-7963-8706 https://orcid.org/0000-0003-4255-0492 |
| _version_ | 1826189376619544576 |
|---|---|
| author | Upadhyay, Urvashi M. Tyler, Betty Patta, Yoda Wicks, Robert Scott, Alexander Masi, Byron Hwang, Lee Grossman, Rachel Brem, Henry Cima, Michael J. Langer, Robert S Spencer, Kevin C |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Upadhyay, Urvashi M. Tyler, Betty Patta, Yoda Wicks, Robert Scott, Alexander Masi, Byron Hwang, Lee Grossman, Rachel Brem, Henry Cima, Michael J. Langer, Robert S Spencer, Kevin C |
| author_sort | Upadhyay, Urvashi M. |
| collection | MIT |
| description | Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood–brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source. |
| first_indexed | 2024-09-23T08:13:46Z |
| format | Article |
| id | mit-1721.1/96952 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:13:46Z |
| publishDate | 2015 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/969522022-09-30T08:26:52Z Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain Upadhyay, Urvashi M. Tyler, Betty Patta, Yoda Wicks, Robert Scott, Alexander Masi, Byron Hwang, Lee Grossman, Rachel Brem, Henry Cima, Michael J. Langer, Robert S Spencer, Kevin C Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Materials Science and Engineering Koch Institute for Integrative Cancer Research at MIT Patta, Yoda Spencer, Kevin C. Scott, Alexander Masi, Byron Cima, Michael J. Langer, Robert Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood–brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source. National Institutes of Health (U.S.) (Grant R01 EB006365-06) Brain Science Foundation (Private Grant 106708) 2015-05-11T14:05:17Z 2015-05-11T14:05:17Z 2014-11 2012-08 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/96952 Upadhyay, Urvashi M., Betty Tyler, Yoda Patta, Robert Wicks, Kevin Spencer, Alexander Scott, Byron Masi, et al. “Intracranial Microcapsule Chemotherapy Delivery for the Localized Treatment of Rodent Metastatic Breast Adenocarcinoma in the Brain.” Proceedings of the National Academy of Sciences 111, no. 45 (October 27, 2014): 16071–16076. https://orcid.org/0000-0003-2379-6139 https://orcid.org/0000-0002-7963-8706 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1073/pnas.1313420110 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | Upadhyay, Urvashi M. Tyler, Betty Patta, Yoda Wicks, Robert Scott, Alexander Masi, Byron Hwang, Lee Grossman, Rachel Brem, Henry Cima, Michael J. Langer, Robert S Spencer, Kevin C Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain |
| title | Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain |
| title_full | Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain |
| title_fullStr | Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain |
| title_full_unstemmed | Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain |
| title_short | Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain |
| title_sort | intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain |
| url | http://hdl.handle.net/1721.1/96952 https://orcid.org/0000-0003-2379-6139 https://orcid.org/0000-0002-7963-8706 https://orcid.org/0000-0003-4255-0492 |
| work_keys_str_mv | AT upadhyayurvashim intracranialmicrocapsulechemotherapydeliveryforthelocalizedtreatmentofrodentmetastaticbreastadenocarcinomainthebrain AT tylerbetty intracranialmicrocapsulechemotherapydeliveryforthelocalizedtreatmentofrodentmetastaticbreastadenocarcinomainthebrain AT pattayoda intracranialmicrocapsulechemotherapydeliveryforthelocalizedtreatmentofrodentmetastaticbreastadenocarcinomainthebrain AT wicksrobert intracranialmicrocapsulechemotherapydeliveryforthelocalizedtreatmentofrodentmetastaticbreastadenocarcinomainthebrain AT scottalexander intracranialmicrocapsulechemotherapydeliveryforthelocalizedtreatmentofrodentmetastaticbreastadenocarcinomainthebrain AT masibyron intracranialmicrocapsulechemotherapydeliveryforthelocalizedtreatmentofrodentmetastaticbreastadenocarcinomainthebrain AT hwanglee intracranialmicrocapsulechemotherapydeliveryforthelocalizedtreatmentofrodentmetastaticbreastadenocarcinomainthebrain AT grossmanrachel intracranialmicrocapsulechemotherapydeliveryforthelocalizedtreatmentofrodentmetastaticbreastadenocarcinomainthebrain AT bremhenry intracranialmicrocapsulechemotherapydeliveryforthelocalizedtreatmentofrodentmetastaticbreastadenocarcinomainthebrain AT cimamichaelj intracranialmicrocapsulechemotherapydeliveryforthelocalizedtreatmentofrodentmetastaticbreastadenocarcinomainthebrain AT langerroberts intracranialmicrocapsulechemotherapydeliveryforthelocalizedtreatmentofrodentmetastaticbreastadenocarcinomainthebrain AT spencerkevinc intracranialmicrocapsulechemotherapydeliveryforthelocalizedtreatmentofrodentmetastaticbreastadenocarcinomainthebrain |