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<p>Local drug delivery systems (LDDS) are a promising method to overcome challenges associated with chemotherapeutic treatment of brain tumours, namely poor blood-brain barrier penetration. Here we report a poly(ethyleneglycol)-poly(lactide)-poly(caprolactone)-poly(lactide)-poly(ethyleneglycol) based injectable hydrogel, PELCLE, loaded with Doxorubicin (Dox) and Olaparib (Ola) as an LDDS against glioblastoma (GBM), a primary malignant brain tumour with a poor prognosis. The thermoresponsive properties of the hydrogel, which behaved as a liquid at room temperature and formed a gel at elevated temperatures, were not impacted by the inclusion of chemotherapeutics whereby two-week sustained release was recorded for both Dox and Ola. Drug potency was assessed against a panel of GBM cell lines, both a syngeneic mouse line and primary patient-derived lines, and the combination of Dox/Ola demonstrated synergistic effects at a range of drug: drug ratios. The application of radiotherapy (XRT) in combination with Dox/Ola improved treatment efficacy both in vitro and in vivo, with a significant increase in median survival observed when Dox/Ola PELCLE hydrogels were applied against a surgical resection model of GBM (syngeneic mouse model SB28) with and without the addition of adjuvant XRT (28 and 23 days, respectively, <i>p</i> &lt; 0.01). Furthermore, a long-term survivor was noted in the group treated with the drug loaded HG and XRT, which was associated with a very small residual tumour, indicating the efficacy of this treatment against a GBM in vivo model.</p>

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Local delivery of Doxorubicin and Olaparib loaded injectable hydrogels with adjuvant radiotherapy improves survival in a glioblastoma in vivo model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月23日

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  • Robert Cavanagh,
  • Gary Shaw,
  • Phoebe McCrorie,
  • Amr ElSherbenny,
  • Alina Pandele,
  • Supisara Jearranaiprepame,
  • Bayan Ghanem,
  • Natalie Allcock,
  • Heiko Wurdak,
  • Ryan K. Mathew,
  • Cameron Alexander,
  • Ruman Rahman,
  • Cara Moloney

摘要

Local drug delivery systems (LDDS) are a promising method to overcome challenges associated with chemotherapeutic treatment of brain tumours, namely poor blood-brain barrier penetration. Here we report a poly(ethyleneglycol)-poly(lactide)-poly(caprolactone)-poly(lactide)-poly(ethyleneglycol) based injectable hydrogel, PELCLE, loaded with Doxorubicin (Dox) and Olaparib (Ola) as an LDDS against glioblastoma (GBM), a primary malignant brain tumour with a poor prognosis. The thermoresponsive properties of the hydrogel, which behaved as a liquid at room temperature and formed a gel at elevated temperatures, were not impacted by the inclusion of chemotherapeutics whereby two-week sustained release was recorded for both Dox and Ola. Drug potency was assessed against a panel of GBM cell lines, both a syngeneic mouse line and primary patient-derived lines, and the combination of Dox/Ola demonstrated synergistic effects at a range of drug: drug ratios. The application of radiotherapy (XRT) in combination with Dox/Ola improved treatment efficacy both in vitro and in vivo, with a significant increase in median survival observed when Dox/Ola PELCLE hydrogels were applied against a surgical resection model of GBM (syngeneic mouse model SB28) with and without the addition of adjuvant XRT (28 and 23 days, respectively, p < 0.01). Furthermore, a long-term survivor was noted in the group treated with the drug loaded HG and XRT, which was associated with a very small residual tumour, indicating the efficacy of this treatment against a GBM in vivo model.