title: Hot melt extruded and injection moulded disulfiram-loaded PLGA millirods for the treatment of glioblastoma multiforme via stereotactic injection.
abstract: Glioblastoma multiforme (GBM) has a poor prognosis and is one of the most common primary malignant brain tumours in adults. Stereotactic injections have been used to deliver chemotherapeutic drugs directly into brain tumours. This paper describes the development of disulfiram (DSF)-loaded biodegradable millirods manufactured using hot melt extrusion (HME) and injection moulding (IM). The paper demonstrates that the stability of the DSF within the millirods is dependent on the manufacturing technique used as well as the drug loading. The physical state of the DSF within the millirods was dependent on the fabrication process, with the DSF in the HME millirods being either completely amorphous within the PLGA, while the DSF within the IM millirods retained between 54 and 66% of its crystallinity. Release of DSF from the millirods was dependent on the degradation rate of the PLGA, the manufacturing technique used as well as the DSF loading. DSF in the 10% (w/w) DSF loaded HME millirods and the 20% (w/w) DSF-loaded HME and IM millirods had a similar cytotoxicity against a GBM cell line compared to the unprocessed DSF control. However, the 10% (w/w) DSF-loaded IM millirods had a significantly lower cytotoxicity when compared to the unprocessed control.
authors.affiliation: Department of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK. Electronic address: C.Mcconville@wlv.ac.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: McConville
authors.affiliation: Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Tawari
authors.affiliation: Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Wang
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004221:Disulfiram / Q000737:chemistry* / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005615:Freezing; D005909:Glioblastoma / Q000188:drug therapy*; D006358:Hot Temperature; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004221:Disulfiram
keywords: Brain tumours; Disulfiram; Hot melt extrusion; Injection moulding and stereotactic injection; PLGA