Development and in vivo evaluation of Irinotecan-loaded Drug Eluting Seeds (iDES) for the localised treatment of recurrent glioblastoma multiforme

Research output: Contribution to journalArticlepeer-review

Standard

Development and in vivo evaluation of Irinotecan-loaded Drug Eluting Seeds (iDES) for the localised treatment of recurrent glioblastoma multiforme. / Gawley, Matthew ; Almond, Lorna ; Daniel, Senam ; Lastakchi, Sarah; Kaur, Sharnjit; Detta, Allah; Cruickshank, Garth; Miller, Ryan; Hingtgen, Shawn ; Sheets, Kevin ; McConville, Christopher.

In: Journal of Controlled Release, Vol. 324, 10.08.2020, p. 1-16.

Research output: Contribution to journalArticlepeer-review

Harvard

APA

Vancouver

Author

Gawley, Matthew ; Almond, Lorna ; Daniel, Senam ; Lastakchi, Sarah ; Kaur, Sharnjit ; Detta, Allah ; Cruickshank, Garth ; Miller, Ryan ; Hingtgen, Shawn ; Sheets, Kevin ; McConville, Christopher. / Development and in vivo evaluation of Irinotecan-loaded Drug Eluting Seeds (iDES) for the localised treatment of recurrent glioblastoma multiforme. In: Journal of Controlled Release. 2020 ; Vol. 324. pp. 1-16.

Bibtex

@article{764019e2da7948d4a5c7057a0b4ad168,
title = "Development and in vivo evaluation of Irinotecan-loaded Drug Eluting Seeds (iDES) for the localised treatment of recurrent glioblastoma multiforme",
abstract = "Glioblastoma multiforme (GBM) is impossible to fully remove surgically and almost always recurs at the borders of the resection cavity, while systemic delivery of therapeutic drug levels to the brain tumour is limited by the blood-brain barrier. This research describes the development of a novel formulation of Irinotecan-loaded Drug Eluting Seeds (iDES) for insertion into the margin of the GBM resection cavity to provide a sustained high local dose with reduced systemic toxicities. We used primary GBM cells from both the tumour core and Brain Around the Tumour tissue from recurrent GBM patients to demonstrate that irinotecan is more effective than temozolomide. Irinotecan had a 75% response rate, while only 50% responded to temozolomide. With temozolomide the cell viability was never below 80% whereas irinotecan achieved cell viabilities of less than 44%. The iDES were manufactured using a hot melt extrusion process with accurate irinotecan drug loadings and the same cytotoxicity as unformulated irinotecan. The iDES released irinotecan in a sustained fashion for up to 7 days. However, only the 30, 40 and 50% w/w loaded iDES formulations released the 300 to 1000 μg of irinotecan needed to be effective in vivo. The 30 and 40% w/w iDES formulations containing 10% plasticizer and either 60 or 50% PLGA prolonged survival from 27 to 70 days in a GBM xenograft mouse resection model with no sign of tumour recurrence. The 30% w/w iDES formulations showed equivalent toxicity to a placebo in non-tumour bearing mice. This innovative drug delivery approach could transform the treatment of recurrent GBM patients by improving survival and reducing toxicity.",
keywords = "Drug eluting seeds, Glioblastoma, Irinotecan, Local delivery, PLGA, Sustained release",
author = "Matthew Gawley and Lorna Almond and Senam Daniel and Sarah Lastakchi and Sharnjit Kaur and Allah Detta and Garth Cruickshank and Ryan Miller and Shawn Hingtgen and Kevin Sheets and Christopher McConville",
year = "2020",
month = aug,
day = "10",
doi = "10.1016/j.jconrel.2020.05.012",
language = "English",
volume = "324",
pages = "1--16",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Development and in vivo evaluation of Irinotecan-loaded Drug Eluting Seeds (iDES) for the localised treatment of recurrent glioblastoma multiforme

AU - Gawley, Matthew

AU - Almond, Lorna

AU - Daniel, Senam

AU - Lastakchi, Sarah

AU - Kaur, Sharnjit

AU - Detta, Allah

AU - Cruickshank, Garth

AU - Miller, Ryan

AU - Hingtgen, Shawn

AU - Sheets, Kevin

AU - McConville, Christopher

PY - 2020/8/10

Y1 - 2020/8/10

N2 - Glioblastoma multiforme (GBM) is impossible to fully remove surgically and almost always recurs at the borders of the resection cavity, while systemic delivery of therapeutic drug levels to the brain tumour is limited by the blood-brain barrier. This research describes the development of a novel formulation of Irinotecan-loaded Drug Eluting Seeds (iDES) for insertion into the margin of the GBM resection cavity to provide a sustained high local dose with reduced systemic toxicities. We used primary GBM cells from both the tumour core and Brain Around the Tumour tissue from recurrent GBM patients to demonstrate that irinotecan is more effective than temozolomide. Irinotecan had a 75% response rate, while only 50% responded to temozolomide. With temozolomide the cell viability was never below 80% whereas irinotecan achieved cell viabilities of less than 44%. The iDES were manufactured using a hot melt extrusion process with accurate irinotecan drug loadings and the same cytotoxicity as unformulated irinotecan. The iDES released irinotecan in a sustained fashion for up to 7 days. However, only the 30, 40 and 50% w/w loaded iDES formulations released the 300 to 1000 μg of irinotecan needed to be effective in vivo. The 30 and 40% w/w iDES formulations containing 10% plasticizer and either 60 or 50% PLGA prolonged survival from 27 to 70 days in a GBM xenograft mouse resection model with no sign of tumour recurrence. The 30% w/w iDES formulations showed equivalent toxicity to a placebo in non-tumour bearing mice. This innovative drug delivery approach could transform the treatment of recurrent GBM patients by improving survival and reducing toxicity.

AB - Glioblastoma multiforme (GBM) is impossible to fully remove surgically and almost always recurs at the borders of the resection cavity, while systemic delivery of therapeutic drug levels to the brain tumour is limited by the blood-brain barrier. This research describes the development of a novel formulation of Irinotecan-loaded Drug Eluting Seeds (iDES) for insertion into the margin of the GBM resection cavity to provide a sustained high local dose with reduced systemic toxicities. We used primary GBM cells from both the tumour core and Brain Around the Tumour tissue from recurrent GBM patients to demonstrate that irinotecan is more effective than temozolomide. Irinotecan had a 75% response rate, while only 50% responded to temozolomide. With temozolomide the cell viability was never below 80% whereas irinotecan achieved cell viabilities of less than 44%. The iDES were manufactured using a hot melt extrusion process with accurate irinotecan drug loadings and the same cytotoxicity as unformulated irinotecan. The iDES released irinotecan in a sustained fashion for up to 7 days. However, only the 30, 40 and 50% w/w loaded iDES formulations released the 300 to 1000 μg of irinotecan needed to be effective in vivo. The 30 and 40% w/w iDES formulations containing 10% plasticizer and either 60 or 50% PLGA prolonged survival from 27 to 70 days in a GBM xenograft mouse resection model with no sign of tumour recurrence. The 30% w/w iDES formulations showed equivalent toxicity to a placebo in non-tumour bearing mice. This innovative drug delivery approach could transform the treatment of recurrent GBM patients by improving survival and reducing toxicity.

KW - Drug eluting seeds

KW - Glioblastoma

KW - Irinotecan

KW - Local delivery

KW - PLGA

KW - Sustained release

UR - http://www.scopus.com/inward/record.url?scp=85084614581&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2020.05.012

DO - 10.1016/j.jconrel.2020.05.012

M3 - Article

VL - 324

SP - 1

EP - 16

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -