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Recent advances in the delivery of disulfiram: a critical analysis of promising approaches to improve its pharmacokinetic profile and anticancer efficacy.

ABSTRACT: BACKGROUND:Disulfiram (DSF) has a long history of being used as a first-line promising therapy for treatment of alcoholism in human. Besides its prominence in the treatment of alcoholism, extensive investigations have been carried out to explore other biomedical and pharmacological effects of DSF. Amongst other biomedical implications, plenty researches have shown evidence of promising anticancer efficacy of this agent for treatment of wide range of cancers such as breast cancer, liver cancer and lung carcinoma. METHODS:Electronic databases, including Google scholar, PubMed and Web of science were searched with the keywords disulfiram, nanoparticles, cancer, drug delivery systems. RESULT:Despite its excellent anticancer efficacy, the pharmaceutical significance and clinical applicability of DSF are hampered due to poor stability, low solubility, short plasma half-life, rapid metabolism, and early clearance from systemic circulation. Various attempts have been made to eradicate these issues. Nanotechnology based interventions have gained remarkable recognition in improving pharmacokinetic and pharmacodynamic profile of DSF by improving its stability and avoiding its degradation. CONCLUSION:The aim of the present review is to critically analyse all recent developments in designing various nanotechnology-based delivery systems, to ponder their relevance in improving stability, pharmacokinetic and pharmacodynamic profile, and achieving target-specific delivery of this agent to cancer cells to effectively eradicate cancer and abolish its metastasis. Nanotechnology is a novel approach for overcoming such obstacles faced presently, the results obtained so far using different novel drug delivery systems seem to be very promising to increase the stability and half-life of DSF. Graphical abstract Nanocrrier mediated drug delivery systems for disulfiram.

SUBMITTER: Farooq MA

PROVIDER: S-EPMC6895293 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Recent advances in the delivery of disulfiram: a critical analysis of promising approaches to improve its pharmacokinetic profile and anticancer efficacy.

Farooq Muhammad Asim MA Aquib Md M Khan Daulat Haleem DH Hussain Zahid Z Ahsan Anam A Baig Mirza Muhammad Faran Ashraf MMFA Wande Dickson Pius DP Ahmad Muhammad Masood MM Ahsan Hafiz Muhammad HM Jiajie Jiang J Wang Bo B

Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 20191122 2

<h4>Background</h4>Disulfiram (DSF) has a long history of being used as a first-line promising therapy for treatment of alcoholism in human. Besides its prominence in the treatment of alcoholism, extensive investigations have been carried out to explore other biomedical and pharmacological effects of DSF. Amongst other biomedical implications, plenty researches have shown evidence of promising anticancer efficacy of this agent for treatment of wide range of cancers such as breast cancer, liver c ...[more]

PMID: 31758497

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Project description:Copper (Cu) plays a pivotal role in cancer progression by acting as a co-factor that regulates the activity of many enzymes and structural proteins in cancer cells. Therefore, Cu-based complexes have been investigated as novel anticancer metallodrugs and are considered as a complementary strategy for currently used platinum agents with undesirable general toxicity. Due to the high failure rate and increased cost of new drugs, there is a global drive towards the repositioning of known drugs for cancer treatment in recent years. Disulfiram (DSF) is a first-line antialcoholism drug used in clinics for more than 65 yr. In combination with Cu, it has shown great potential as an anticancer drug by targeting a wide range of cancers. The reaction between DSF and Cu ions forms a copper diethyldithiocarbamate complex (Cu(DDC)2 also known as CuET) which is the active, potent anticancer ingredient through inhibition of NF-κB and ubiquitin-proteasome system as well as alteration of the intracellular reactive oxygen species (ROS). Importantly, DSF/Cu inhibits several molecular targets related to drug resistance, stemness, angiogenesis and metastasis and is thus considered as a novel strategy for overcoming tumour recurrence and relapse in patients. Despite its excellent anticancer efficacy, DSF has proven unsuccessful in several cancer clinical trials. This is likely due to the poor stability, rapid metabolism and/or short plasma half-life of the currently used oral version of DSF and the inability to form Cu(DDC)2 at relevant concentrations in tumour tissues. Here, we summarize the scientific rationale, molecular targets, and mechanisms of action of DSF/Cu in cancer cells and the outcomes of oral DSF ± Cu in cancer clinical trials. We will focus on the novel insights on harnessing the immune system and hypoxic microenvironment using DSF/Cu complex and discuss the emerging delivery strategies that can overcome the shortcomings of DSF-based anticancer therapies and provide opportunities for translation of DSF/Cu or its Cu(DDC)2 complex into cancer therapeutics.

Dataset Information

Recent advances in the delivery of disulfiram: a critical analysis of promising approaches to improve its pharmacokinetic profile and anticancer efficacy.

Publications

Recent advances in the delivery of disulfiram: a critical analysis of promising approaches to improve its pharmacokinetic profile and anticancer efficacy.

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