title: 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.affiliation: School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, WV1 1LY, UK.
authors.forename: Iwona
authors.initials: I
authors.lastname: Zembko
authors.forename: Iram
authors.initials: I
authors.lastname: Ahmed
authors.forename: Aneesa
authors.initials: A
authors.lastname: Farooq
authors.forename: Jagdeep
authors.initials: J
authors.lastname: Dail
authors.forename: Patrica
authors.initials: P
authors.lastname: Tawari
authors.forename: Weiguang
authors.initials: W
authors.lastname: Wang
authors.forename: Christopher
authors.initials: C
authors.lastname: Mcconville
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004221:Disulfiram / Q000008:administration & dosage / Q000737:chemistry*; D004304:Dosage Forms; D004337:Drug Carriers; D004355:Drug Stability; D005909:Glioblastoma / Q000188:drug therapy*; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D033362:Powder Diffraction; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D004304:Dosage Forms; D004337:Drug Carriers; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004221:Disulfiram
keywords: PLGA; biodegradable polymers; blood brain barrier; brain tumours; cancer; controlled delivery; disulfiram; implantable device; localised drug delivery