Injectable diblock copolypeptide hydrogel provides platform to deliver effective concentrations of paclitaxel to an intracranial xenograft model of glioblastoma.
<h4>Introduction</h4>Surgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being firs...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0219632 |
| _version_ | 1811167181084295168 |
|---|---|
| author | Matthew C Garrett Timothy M O'Shea Alexander L Wollenberg Alexander M Bernstein Derek Hung Brittany Staarman Horacio Soto Timothy J Deming Michael V Sofroniew Harley I Kornblum |
| author_facet | Matthew C Garrett Timothy M O'Shea Alexander L Wollenberg Alexander M Bernstein Derek Hung Brittany Staarman Horacio Soto Timothy J Deming Michael V Sofroniew Harley I Kornblum |
| author_sort | Matthew C Garrett |
| collection | DOAJ |
| description | <h4>Introduction</h4>Surgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being first line treatment, temozolomide has only limited efficacy.<h4>Methods</h4>The development of injectable hydrogel-based carrier systems allows for the delivery of a wide range of chemotherapeutics that can achieve high local concentrations, thus potentially avoiding systemic side effects and wide-spread neurotoxicity. To test this modality in a realistic environment, we developed a diblock copolypeptide hydrogel (DCH) capable of carrying and releasing paclitaxel, a compound that we found to be highly potent against primary gliomasphere cells.<h4>Results</h4>The DCH produced minimal tissue reactivity and was well tolerated in the immune-competent mouse brain. Paclitaxel-loaded hydrogel induced less tissue damage, cellular inflammation and reactive astrocytes than cremaphor-taxol (typical taxol-carrier) or hydrogel alone. In a deep subcortical xenograft model of glioblastoma in immunodeficient mice, injection of paclitaxel-loaded hydrogel led to local tumor control and improved survival. However, the tumor cells were highly migratory and were able to eventually escape the area of treatment.<h4>Conclusions</h4>These findings suggest this technology may be ultimately applicable to patients with deep-seated inoperable tumors, but as currently formulated, complete tumor eradication would be highly unlikely. Future studies should focus on targeting the migratory potential of surviving cells. |
| first_indexed | 2024-04-10T16:04:51Z |
| format | Article |
| id | doaj.art-7457d913069743f69fa612d3c0099955 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-10T16:04:51Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7457d913069743f69fa612d3c00999552023-02-10T05:31:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01157e021963210.1371/journal.pone.0219632Injectable diblock copolypeptide hydrogel provides platform to deliver effective concentrations of paclitaxel to an intracranial xenograft model of glioblastoma.Matthew C GarrettTimothy M O'SheaAlexander L WollenbergAlexander M BernsteinDerek HungBrittany StaarmanHoracio SotoTimothy J DemingMichael V SofroniewHarley I Kornblum<h4>Introduction</h4>Surgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being first line treatment, temozolomide has only limited efficacy.<h4>Methods</h4>The development of injectable hydrogel-based carrier systems allows for the delivery of a wide range of chemotherapeutics that can achieve high local concentrations, thus potentially avoiding systemic side effects and wide-spread neurotoxicity. To test this modality in a realistic environment, we developed a diblock copolypeptide hydrogel (DCH) capable of carrying and releasing paclitaxel, a compound that we found to be highly potent against primary gliomasphere cells.<h4>Results</h4>The DCH produced minimal tissue reactivity and was well tolerated in the immune-competent mouse brain. Paclitaxel-loaded hydrogel induced less tissue damage, cellular inflammation and reactive astrocytes than cremaphor-taxol (typical taxol-carrier) or hydrogel alone. In a deep subcortical xenograft model of glioblastoma in immunodeficient mice, injection of paclitaxel-loaded hydrogel led to local tumor control and improved survival. However, the tumor cells were highly migratory and were able to eventually escape the area of treatment.<h4>Conclusions</h4>These findings suggest this technology may be ultimately applicable to patients with deep-seated inoperable tumors, but as currently formulated, complete tumor eradication would be highly unlikely. Future studies should focus on targeting the migratory potential of surviving cells.https://doi.org/10.1371/journal.pone.0219632 |
| spellingShingle | Matthew C Garrett Timothy M O'Shea Alexander L Wollenberg Alexander M Bernstein Derek Hung Brittany Staarman Horacio Soto Timothy J Deming Michael V Sofroniew Harley I Kornblum Injectable diblock copolypeptide hydrogel provides platform to deliver effective concentrations of paclitaxel to an intracranial xenograft model of glioblastoma. PLoS ONE |
| title | Injectable diblock copolypeptide hydrogel provides platform to deliver effective concentrations of paclitaxel to an intracranial xenograft model of glioblastoma. |
| title_full | Injectable diblock copolypeptide hydrogel provides platform to deliver effective concentrations of paclitaxel to an intracranial xenograft model of glioblastoma. |
| title_fullStr | Injectable diblock copolypeptide hydrogel provides platform to deliver effective concentrations of paclitaxel to an intracranial xenograft model of glioblastoma. |
| title_full_unstemmed | Injectable diblock copolypeptide hydrogel provides platform to deliver effective concentrations of paclitaxel to an intracranial xenograft model of glioblastoma. |
| title_short | Injectable diblock copolypeptide hydrogel provides platform to deliver effective concentrations of paclitaxel to an intracranial xenograft model of glioblastoma. |
| title_sort | injectable diblock copolypeptide hydrogel provides platform to deliver effective concentrations of paclitaxel to an intracranial xenograft model of glioblastoma |
| url | https://doi.org/10.1371/journal.pone.0219632 |
| work_keys_str_mv | AT matthewcgarrett injectablediblockcopolypeptidehydrogelprovidesplatformtodelivereffectiveconcentrationsofpaclitaxeltoanintracranialxenograftmodelofglioblastoma AT timothymoshea injectablediblockcopolypeptidehydrogelprovidesplatformtodelivereffectiveconcentrationsofpaclitaxeltoanintracranialxenograftmodelofglioblastoma AT alexanderlwollenberg injectablediblockcopolypeptidehydrogelprovidesplatformtodelivereffectiveconcentrationsofpaclitaxeltoanintracranialxenograftmodelofglioblastoma AT alexandermbernstein injectablediblockcopolypeptidehydrogelprovidesplatformtodelivereffectiveconcentrationsofpaclitaxeltoanintracranialxenograftmodelofglioblastoma AT derekhung injectablediblockcopolypeptidehydrogelprovidesplatformtodelivereffectiveconcentrationsofpaclitaxeltoanintracranialxenograftmodelofglioblastoma AT brittanystaarman injectablediblockcopolypeptidehydrogelprovidesplatformtodelivereffectiveconcentrationsofpaclitaxeltoanintracranialxenograftmodelofglioblastoma AT horaciosoto injectablediblockcopolypeptidehydrogelprovidesplatformtodelivereffectiveconcentrationsofpaclitaxeltoanintracranialxenograftmodelofglioblastoma AT timothyjdeming injectablediblockcopolypeptidehydrogelprovidesplatformtodelivereffectiveconcentrationsofpaclitaxeltoanintracranialxenograftmodelofglioblastoma AT michaelvsofroniew injectablediblockcopolypeptidehydrogelprovidesplatformtodelivereffectiveconcentrationsofpaclitaxeltoanintracranialxenograftmodelofglioblastoma AT harleyikornblum injectablediblockcopolypeptidehydrogelprovidesplatformtodelivereffectiveconcentrationsofpaclitaxeltoanintracranialxenograftmodelofglioblastoma |