Clinical, pharmacological, and formulation evaluation of disulfiram in the treatment of glioblastoma-a systematic literature review

Introduction: Glioblastoma (GB) is one of the most challenging central nervous system (CNS) tumors in treatment options and response, urging the development of novel management strategies. The anti-alcoholism drug, disulfiram (DS), has a potential anticancer activity, and its complex mechanism of action is assumed to be well exploited against the heterogeneous GB.Area covered: Through a systematic literature review about repositioning DS to GB treatment, an evaluation of the clinical, pharmacological, and formulation strategies is provided to specify the challenges of drug delivery and thus to advance its clinical translation. From six databases, 35 articles were selected, including case report (1); clinical trials (3); original articles mainly representing in vitro and preclinical pharmacological data, and 10 dealing with technological approaches.Expert opinion: The repositioning of DS in GB treatment is facing drug and tumor-associated limitations due to the oral drug's low bioavailability, unwanted metabolism, and inefficient delivery to brain-tumor tissue. Development strategies using molecular encapsulation of DS and the parenteral dosage forms improve the anticancer pharmacology of the drug. The development of optimized drug delivery systems (DDS) shows promise for the clinical translation of DS into GB adjuvant therapy.