gliadelwafer-a brain tumour targetting drug delivery system

GLIADEL ®: 

GLIADEL ® A Novel Brain Tumor Targeting Drug Delivery System

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It is the small disc shaped synthetic, biodegradable implant containing the anti-neoplastic agent CARMUSTINE (BCNU) used in brain tumors. GLIADEL® Wafer is the first implantable polymer drug delivery system(DDS) ,approved by FDA for the clinical use in the brain tumors. The goal of GLIADEL® Wafer therapy is to eradicate the brain tumor cells left behind post tumor surgery, thereby extending survival probability in GlioBlastoma multiforme (GBM).

GlioBlastoma Multiforme : 

GlioBlastoma Multiforme GBM is most common malignant primary brain tumor involving glial cells. Recently a viral cause has been discovered possibly SV40 and cytomegalovirus. GBM tumors are characterized by presence of small area of necrotizing tissue that is surrounded by anaplastic cell.

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Tumors of the brain Normal brain

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Uncompleted removal of the tumors Time delay GBM Treatment Non-Pharmacological Approach

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  Tumors And also in the Healthy cells Because of the INABILITY TO CROSS BBB SEVERE SIDE EFFECTS due to the L ack of the selectivity GBM Treatment Pharmacological Approach

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CARMUSTINE Net outcome: PRONOUNCED SYSTEMIC TOXIITY GBM Treatment Pharmacological Approach 

GLIADEL ®: 

Product Company Gliadel Wafer 7.7mg Guilford Pharmaceuticals Inc Gliadel Wafer 7.7mg MGI Pharma a Division of Eisai Inc Wt.:200mg Active Ingredients: Carmustine 7.7mg Other Names: Gliadel Rx Status: Available by prescription only Generic Available: No Descriptions:Impant R x GLIADEL ®

GLIADEL ® Composition : 

GLIADEL ® Composition API Polymer

WORKING AND MECHANISM Over-all Process : 

WORKING AND MECHANISM Over-all Process Gliadel Wafer #2.Implanting of the wafers into tumor site #1. Gliade Wafer (sterilized) #3. Gliadel starts dissolving Carmustine molecules Tumor cell Gliadel Wafer

WORKING AND MECHANISM : 

#4. Drug molecules gets released . Gliadel Wafer Destruction of the TUMOR cells Brain tumor Carmustine molecules Magnification SEM(scanning Electron. Microscopy) Over-all Process WORKING AND MECHANISM

EVALUATION Erosion Pattern : 

morphological changes of the polymer after implanted in the tumor cavity Scanning electron microscopy (SEM) was used The porosity of the wafer fabricated from spray dried polymer gradually increased during erosion. The eroding front gradually advanced from the surface to the interior of the wafer in a layer wise fashion , creating pores and connecting channel Eventually both the interior and exterior of the wafers were eroded and the same porous structure was seen throughout the whole wafer EVALUATION Erosion Pattern

Drug Release : 

Drug Release Method of evaluation: By using quantitative autoradiography and thin-layer chromatography, tumoricidal drug concentrations were detected. In the laboratory, BCNU polymer preparations have been shown to release active drug in rat and rabbit brain for up to three weeks minimum after implantation.

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Pharmacokinetic studies in nonhuman primates ( cynomolgus monkeys) with 20%-loaded BCNU polyanhydride polymer showed that BCNU concentrations in the brain achieved by polymeric delivery were four to 1,200 times higher than that produced by intravenous administration of drug. This is enough to destroy the tumors effectively. Therapy Life Expectancy (weeks) None 4 Surgery 15 Surgery + Radiation 16 Surgery +Radiation +Gliadel ® 50 EVALUATION Therapeutic Efficacy

SAFETY INFORMATION: 

SAFETY INFORMATION Contra-indicaion: hypersensitivity to carmustine. Adverse Events: Seizures, Brain edema, Intracranial infection .

FUTURE APPLICATION: 

FUTURE APPLICATION Radioresistant metastatic brain tumors. Intracranial metastatic melanoma Colon cancer, lung cancer, breast, and renal cell carcinoma

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