Biodegradable polymer implants to treat brain tumors

Brem, Henry; Gabikian, Patrik

doi:10.1016/s0168-3659(01)00311-x

Cited by 174 publications

(105 citation statements)

References 19 publications

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“…Controlledrelease polymers allow for local, sustained, and tightly regulated drug delivery to the CNS with reproducible release kinetics. 27,28 The development and clinical application of carmustine-loaded polymers have demonstrated the effectiveness of local chemotherapy against malignant gliomas in experimental models 12 and ongoing clinical trials. 13,14,28 The use of polymer matrices to deliver pharmacotherapy interstitially to the CNS has also been accomplished in experimental models of neurodegenerative disorders, 29 brain edema, 30 and chronic posthemorrhagic vasospasm.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Experimental Cerebral Vasospasm by Intracranial Delivery of a Nitric Oxide Donor From a Controlled-Release Polymer

Gabikian

Clatterbuck

Eberhart

et al. 2002

Stroke

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Background and Purpose-A reduction in the local availability of nitric oxide (NO) may play a role in the etiology of chronic cerebral vasospasm after subarachnoid hemorrhage (SAH). We investigated the toxicity and efficacy of a locally delivered NO donor from a controlled-release polymer in preventing experimental cerebral vasospasm in rats and rabbits, respectively. Methods-Diethylenetriamine/NO (DETA/NO) was incorporated into controlled release ethylene-vinyl acetate (EVAc) polymers. Twenty-eight rats were used in a dose-escalation toxicity study to establish a maximally tolerated dose of DETA/NO-EVAc polymer. In the efficacy experiment, 20 rabbits were assigned to 4 experimental groups (nϭ5 per group): sham operation; SAH only; SAHϩempty EVAc polymer; and SAHϩDETA/NO-EVAc polymer. Treatment was initiated 30 minutes after blood deposition. Basilar artery lumen patency was assessed 72 hours after hemorrhage to evaluate the efficacy of DETA/NO in preventing cerebral vasospasm. Results-In the toxicity study, a dose of 3.4 mg/kg was identified as the LD 20 (dose with 20% mortality during the study period) of this DETA/NO formulation. Brain histology revealed hemorrhage and ischemic changes at the implantation site associated with high concentrations of DETA/NO. In the efficacy study, treatment with DETA/NO-EVAc polymer resulted in a significant decrease in basilar artery vasospasm compared with no treatment (

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Section: Discussionmentioning

confidence: 99%

Prevention of Experimental Cerebral Vasospasm by Intracranial Delivery of a Nitric Oxide Donor From a Controlled-Release Polymer

Gabikian

Clatterbuck

Eberhart

et al. 2002

Stroke

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“…13,14 Biopolymer tech-nology has allowed chemotherapeutic agents to be placed and gradually released at the brain surface subsequent to tumor resection, providing higher local concentrations than possible via systemic delivery, without the associated systemic toxicity. [15][16][17] Depending on the biopolymer composition, drugs can be delivered in a controlled manner for a finite period of time. Unfortunately, reoperation is required for re-dosing of the patient with these biopolymers, and controversy remains over cost and associated morbidities.…”

Section: Introductionmentioning

confidence: 99%

Image-Guided Convection-Enhanced Delivery Platform in the Treatment of Neurological Diseases

et al. 2008

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Summary: Convection-enhanced delivery (CED) of substances within the human brain is becoming a more frequent experimental treatment option in the management of brain tumors, and more recently in phase 1 trials for gene therapy in Parkinson's disease (PD). Benefits of this intracranial drugtransfer technology include a more efficient delivery of large volumes of therapeutic agent to the target region when compared with more standard delivery approaches (i.e., biopolymers, local infusion). In this article, we describe specific technical modifications we have made to the CED process to make it more effective. For example, we developed a reflux-resistant infusion cannula that allows increased infusion rates to be used. We also describe our efforts to visualize the CED process in vivo, using liposomal nanotechnology and real-time intraoperative MRI. In addition to carrying the MRI contrast agent, nanoliposomes also provide a standardized delivery vehicle for the convection of drugs to a specific brain-tissue volume. This technology provides an added level of assurance via visual confirmation of CED, allowing intraoperative alterations to the infusion if there is reflux or aberrant delivery. We propose that these specific modifications to the CED technology will improve efficacy by documenting and standardizing the treatment-volume delivery. Furthermore, we believe that this image-guided CED platform can be used in other translational neuroscience efforts, with eventual clinical application beyond neuro-oncology and PD.

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“…In the field of local delivery, carmustine-loaded Gliadel wafer (Guilford Pharmaceuticals, Baltimore, MD) fabricated from poly(carboxyphenoxy propane:sebacic acid) proved very promising in clinical trials for the treatment of malignant glioma, increasing both survival and safety. 16 The objective of this study was to develop a chitosan film-based local delivery system for sustained release of paclitaxel to tumor site after implantation. These films have been evaluated for the release of impregnated paclitaxel, characterized by physical techniques and microscopy, and examined for inflammatory reactions by histological examination after implantation in mice.…”

Section: Introductionmentioning

confidence: 99%

Development and characterization of biodegradable chitosan films for local delivery of paclitaxel

Dhanikula

Panchagnula

2004

AAPS J

103

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Intratumoral and local drug delivery strategies have gained momentum recently as a promising modality in cancer therapy. In order to deliver paclitaxel at the tumor site in therapeutically relevant concentrations, chitosan films were fabricated. Paclitaxel could be loaded at 31% wt/wt in films, which were translucent and flexible. Physicochemical characterization of paclitaxel via thermal, spectroscopic, x-ray diffraction, and electron microscopy techniques revealed information on solid-state properties of paclitaxel as well as chitosan in films. While chitosan was in amorphous form, paclitaxel seemed to be present in both amorphous and crystalline forms in film. The polymeric dispersion of paclitaxel in poloxamer formed fibrous structures generating discontinuities in the film matrix, thereby leading to the introduction of perturbations in the packing arrangement of polymer chains. These films released only 10% to 15% of loaded paclitaxel by a burst effect under in vitro testing conditions, with lysozyme having no effect on the release. However, films softened after implantation in mice and lost integrity over time. The implantable delivery system is not only biodegradable but also well tolerated in vivo and hence, biocompatible as revealed by histological studies. The lack of formulation-induced local inflammatory responses of paclitaxel chitosan films suggests a new paradigm for localized chemotherapy based on implantable systems.

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Biodegradable polymer implants to treat brain tumors

Cited by 174 publications

References 19 publications

Prevention of Experimental Cerebral Vasospasm by Intracranial Delivery of a Nitric Oxide Donor From a Controlled-Release Polymer

Prevention of Experimental Cerebral Vasospasm by Intracranial Delivery of a Nitric Oxide Donor From a Controlled-Release Polymer

Image-Guided Convection-Enhanced Delivery Platform in the Treatment of Neurological Diseases

Development and characterization of biodegradable chitosan films for local delivery of paclitaxel

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