Intracranial microcapsule drug delivery device for the treatment of an experimental gliosarcoma model

Scott, Alexander W.; Tyler, Betty; Masi, Byron C.; Upadhyay, Urvashi; Patta, Yoda Rante; Grossman, Rachel; Basaldella, Luca; Langer, Robert; Brem, Henry; Cima, Michael J.

doi:10.1016/j.biomaterials.2010.12.020

Cited by 77 publications

(63 citation statements)

References 29 publications

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“…The clinical focus of CNS drug delivery has been high-grade glioma (12). The modest increases in survival seen with such strategies have been attributed, in part, to the limited efficacy of the chemotherapies used and the disease target itself, because these tumors are among the most infiltrative and aggressive tumors studied (6,8).…”

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confidence: 99%

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Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Upadhyay

Tyler

Patta³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Brain metastases represent the most common intracranial tumors in adults. Adequate chemotherapy delivery to the CNS is hindered by the blood–brain barrier. Efforts in intracranial chemotherapy delivery aim to maximize CNS levels while minimizing systemic toxicity; however, the success has been limited thus far. In this work, intracranial implanted doxorubicin and temozolomide microcapsules are compared with systemic administration in a novel rodent model of breast adenocarcinoma brain metastases. These microcapsules are versatile and efficacious, but that efficacy may depend on the ability of the chemotherapy to diffuse in brain tissue. These insights apply to other non-CNS applications of local drug delivery, and drugs should be evaluated based on their ability to penetrate the targeted tissue as well as their inherent efficacy.

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confidence: 99%

“…Several experiments have been conducted with polymer-based vehicles, which locally delivery chemotherapy, that suggest their efficacy in brain metastases (13). The microcapsules described here were studied in a rodent glioma model and showed tunable release kinetics and efficacy (12). These vehicles have, however, not been tested in brain metastases.…”

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confidence: 99%

Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Upadhyay

Tyler

Patta³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…A drug-release microdevice for mice was designed and used to compare the efficacy and toxicity of low but prolonged IP cisplatin exposure (low C max ) to the standard of care of periodic IP cisplatin spikes (high C max ). A single compartment drug delivery device has been previously shown by our group to effectively deliver temozolomide at a constant rate intracranially for gliosarcoma treatment in rat models, and a device designed by our group to deliver drugs to the bladder is being evaluated in humans [22,23].…”

Section: Discussionmentioning

confidence: 99%

Sustained, low-dose intraperitoneal cisplatin improves treatment outcome in ovarian cancer mouse models

Tanenbaum

et al. 2015

Journal of Controlled Release

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Intraperitoneal (IP) chemotherapy for ovarian cancer treatment prolongs overall survival by 16 months compared to intravenous chemotherapy but is not widely practiced due to catheter-related complications and complexity of administration. An implantable, nonresorbable IP microdevice was used to release chemotherapeutic agent at a constant rate of approximately 1.3 µg/hour in vitro and 1.0 µg/hour in vivo. Studies conducted in two orthotopic murine models bearing human xenografts (SKOV3 and UCI101) demonstrate that continuous dosing reduces tumor burden to the same extent as weekly IP bolus drug injections. Treatment-induced toxicity was quantified via body weight loss and complete blood count. The microdevice resulted in significantly less toxicity than IP bolus injections, despite administration of higher cumulative doses (total area under the concentration-time curve of 3,049 ng-day/mL with the microdevice vs. 2,118 ng-day/mL with IP bolus injections). This preclinical study supports the concept that reduced toxicity with similar efficacy outcomes can be achieved by continuous dosing in ovarian cancer patients currently treated with IP therapy.

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“…Microchips -miniaturized depot devices -are a viable method for controlling drug delivery to brain tumors, and have the potential to achieve a broad aggregate distribution profile [49,50].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies

Mangraviti¹,

Gullotti²,

Tyler³

et al. 2016

Journal of Controlled Release

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Intracranial microcapsule drug delivery device for the treatment of an experimental gliosarcoma model

Cited by 77 publications

References 29 publications

Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Sustained, low-dose intraperitoneal cisplatin improves treatment outcome in ovarian cancer mouse models

Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies

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