Effects of GLIADEL® wafer initial molecular weight on the erosion of wafer and release of BCNU

Dang, Wenbin; Daviau, Todd; Ying, Peter; Yong, Zhao; Nowotnik, David P.; Clow, Charles S; Tyler, Betty; Brem, Henry

doi:10.1016/0168-3659(96)01371-5

Cited by 78 publications

(38 citation statements)

References 24 publications

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“…First, it is reasonable to assume that the volume of the polymeric implant remains constant over the course of diffusion since the system delivers drug prior to any significant degradation. 17 The simplified models were also able to effectively characterize carmustine distribution over the majority of the disk's initial drug delivery period. 15,16 Compared with the 6 to 8 weeks for the polymeric disk to completely degrade, 23 the implant should experience little to no volume change during the estimated 30 days it takes for the polymer to deliver 90% of its payload.…”

Section: Discussion On the Limitations Of Simple Modelsmentioning

confidence: 99%

“…The effective diffusion coefficient for transport through the polymer was empirically determined to be 6.7 × 10 −10 cm 2 /s, a reasonable value for a small-molecule drug in Polifeprosan 20. Dang and coworkers 17 also noted that in vivo studies of carmustine release from normal rat brains showed a linear relationship between the cumulative drug release rate and the square root of time for approximately the first 10 h after implantation. In summary, the above equations can be applied to describe the drug release of carmustine from Gliadel wafers during early times when the drug is released primarily by diffusion through the polymer matrix.…”

Section: Drug Release From a Monolithic Slabmentioning

confidence: 99%

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Modeling Mass Transfer from Carmustine-Loaded Polymeric Implants for Malignant Gliomas

et al. 2014

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Section: Discussion On the Limitations Of Simple Modelsmentioning

confidence: 99%

Section: Drug Release From a Monolithic Slabmentioning

confidence: 99%

Modeling Mass Transfer from Carmustine-Loaded Polymeric Implants for Malignant Gliomas

et al. 2014

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“…The wafers are composed of a degradable, polymeric matrix of 1,3-bis(p-carboxyphenoxy)propane and sebacic acid in a 20 to 80 molar ratio loaded with 7.7 mg carmustine [9]. Combined with tumor resection and radiation therapy, the GLIADEL® wafers increased patient survival by approximately two months and are a current standard of care for brain tumor patients [10].…”

Section: Surgical Excision Radiation Therapy and Chemotherapymentioning

confidence: 99%

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Floyd

Galperin

Ratner

2015

J Biomedical Materials Res

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Departments of Bioengineering and Chemical EngineeringThe grim prognosis for patients diagnosed with malignant gliomas necessitates the development of new therapeutic strategies for localized and sustained drug delivery to combat tumor drug resistance and regrowth. Here we introduced the novel formulation of drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy (DREAM BIG Therapy) that is applied post-resection. DREAM BIG Therapy consists of three types of microspheres [poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), and poly(ε-caprolactone) (PCL)] containing various encapsulated chemotherapeutics, suspended in a degradable, aqueous poly(Nisopropylacrylamide) (PNIPAM) solution. The thermoresponsive PNIPAM solution is capable of suspending drug encapsulated microspheres at room temperature which can be "sprayed on" the post-surgical site. The physiological temperature of the treatment site (37°C) would cause PNIPAM solution to solidify and form an adherent gel layer with entrapped microspheres, providing intimate contact with remaining tumor cells. Over time, PLGA (rapid degradation), PLA (medium speed degradation), and then PCL (slow degradation) microspheres would break iv down, releasing their drug payloads in a sequential, multi-drug release directly to the tumor site, addressing cancerous regrowth and tumor drug resistance. This dissertation will address the development of DREAM BIG Therapy, from microsphere formulation to pilot in vivo studies.Initial work focused on developing blank and drug encapsulated microspheres using emulsion techniques. Preliminary studies utilized rhodamine B as a model drug for encapsulation in PLGA, PLA, and PCL particles and optimized formulation parameters to achieve a high encapsulation. Then, gefitinib, IgG, and lomustine were encapsulated in PLGA, PLA, and PCL microspheres, respectively, achieving encapsulation efficiencies greater than 80% and drug loadings greater than 0.3%. The in vitro release of gefitinib and IgG were also studied. Gefitinib released from PLGA microspheres over 40 days while the release of IgG from PLA microspheres was slower, over a year long period.The microsphere-PNIPAM system was tested for aerosolized application ex vivo. The aqueous PNIPAM solution suspended the microspheres and was aerosolized before phase transitioning to an adherent gel layer on the tissue, entrapping the microspheres on the tissue surface. Finally, when tested in vivo, the gefitinib encapsulated PLGA microspheres entrapped in PNIPAM slowed the tumor volume growth of a subcutaneous C6 glioma in comparison to blank PLGA microspheres entrapped in PNIPAM. Overall, this research confirms the potential of DREAM BIG therapy for future use with multiple chemotherapeutics and microsphere types to combat gliomas at a localized site.v

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“…Measuring the release of hydroxycamptothecin involved placing a hydroxycamptothecin-loaded polymer disc into a vial with 10 ml of 0.1 M phosphate-buffered saline containing 1% sodium dodecyl sulfonate (SDS), pH 6.5, and incubating at 37˚C [10]. The solution was removed at various time points and replaced with fresh buffer, and the recovered solution was assayed for the presence of hydroxycamptothecin by high-pressure liquid chromatography (HPLC).…”

Section: Assays Of Hydroxycamptothecin Release From Polymersmentioning

confidence: 99%

Polymer Delivery of Hydroxycamptothecin against C6 Glioma

Hu¹,

Tang²,

Liu³

2014

JCT

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Hydroxycamptothecin is a potent antineoplastic agent that has shown efficacy against multiple tumor lines in vitro. This is the first study to investigate the release, distribution, and efficacy of hydroxycamptothecin which was incorporated into the biodegradable polymer Polylactic Acid (PLA), and implant into brain directly. In vitro release curve generated showed that a large initial release occurred over the first three days and was followed by a steady, but considerably slower rate of release over the next 25 days. After implanting the discs into 40 male SD rats, the animals were followed up to 28 days, where the concentration in brain tissue was far higher than that in peripheral blood at the each of the eight time-points evaluated, and it was also within the therapeutic range for C6 cells tested in vitro. The in vivo efficacy of the discs was evaluated with rats inoculated intracranially with C6 glioma and treated with hydroxycamptothecin polymer compared to intravenous as well as intratumoral injections; the median survival is 21.1, 13.9, 14.9 days, respectively. Given these data, we conclude that the biodegradable polymer PLA releases hydroxycamptothecin, producing tumoricidal levels in brain tissues and prolonging survival in a rat glioma model.

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Effects of GLIADEL® wafer initial molecular weight on the erosion of wafer and release of BCNU

Cited by 78 publications

References 24 publications

Modeling Mass Transfer from Carmustine-Loaded Polymeric Implants for Malignant Gliomas

Modeling Mass Transfer from Carmustine-Loaded Polymeric Implants for Malignant Gliomas

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Polymer Delivery of Hydroxycamptothecin against C6 Glioma

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