Development of disulfiram-loaded poly(lactic-co-glycolic acid) wafers for the localised treatment of glioblastoma multiforme: a comparison of manufacturing techniques.

Abstract

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumour in adults with a very poor prognosis. This paper describes the development of disulfiram (DSF)-loaded biodegradable wafers manufactured using three standard techniques: compression, solvent casting and heat compression moulding. The paper demonstrates that neither technique has an adverse effect on the stability of the DSF within the wafers. However, the solvent casting technique results in an interaction between the poly(lactic-co-glycolic acid) (PLGA) and the DSF. The physical state of the DSF within the wafers was dependent on the manufacturing technique, with the DSF in the wafers manufactured by compression or solvent casting retaining between 40% and 98% crystallinity, whereas the DSF in the wafers manufactured using heat compression moulding was completely amorphous. Release of DSF from the wafers is dependent on the degradation of the PLGA, the manufacturing technique used, and the DSF loading. DSF in the compressed and heat compression moulded wafers had a similar cytotoxicity against a GBM cell line compared with the unprocessed DSF control. However, the cytotoxicity of the DSF in the solvent-casted wafers was significantly lower than the unprocessed DSF.

• Authors: Iwona Zembko, Iram Ahmed, Aneesa Farooq, Jagdeep Dail, Patrica Tawari, Weiguang Wang, Christopher Mcconville
• Journal: Journal of pharmaceutical sciences (J Pharm Sci) Vol. 104 Issue 3 Pg. 1076-86 (Mar 2015) ISSN: 1520-6017 [Electronic] United States
• PMID: 25537972 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Chemical References

• Antineoplastic Agents
• Dosage Forms
• Drug Carriers
• Solvents
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Disulfiram

Topics

• Antineoplastic Agents (administration & dosage, chemistry)
• Brain Neoplasms (drug therapy)
• Calorimetry, Differential Scanning
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chemistry, Pharmaceutical
• Crystallography, X-Ray
• Disulfiram (administration & dosage, chemistry)
• Dosage Forms
• Drug Carriers
• Drug Stability
• Glioblastoma (drug therapy)
• Hot Temperature
• Humans
• Kinetics
• Lactic Acid (chemistry)
• Microscopy, Electron, Scanning
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Powder Diffraction
• Solubility
• Solvents (chemistry)
• Surface Properties
• Technology, Pharmaceutical (methods)