Integrating the drug, disulfiram into the vitamin E-TPGS-modified PEGylated nanostructured lipid carriers to synergize its repurposing for anti-cancer therapy of solid tumors

Banerjee, Parikshit; Geng, Tianjiao; Mahanty, Arpan; Li, Tiantian; Zong, Li; Wang, Bo

doi:10.1016/j.ijpharm.2018.12.051

Cited by 42 publications

(19 citation statements)

References 96 publications

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“…Another group has developed an encapsulated formulation of DSF and doxorubicin which reduced the expression of P-gp and increased the efficacy of doxorubicin in breast cancer cells (Rolle et al, 2020). Banerjee et al (2019) has shown that a formulation of nanostructured lipid carriers (NLC) encapsulated DSF modified with d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E-TPGS) showed an enhanced uptake in breast cancer cell lines and significantly reduced the tumour size and enhanced tumour suppression in xenografted mouse models (Banerjee et al, 2019).…”

Section: Nanotechnology-based Formulation Strategies For Delivery Of Disulfirammentioning

confidence: 99%

Recent Advances in Repurposing Disulfiram and Disulfiram Derivatives as Copper-Dependent Anticancer Agents

Kannappan

Ali

Small

et al. 2021

Front. Mol. Biosci.

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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.

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Section: Nanotechnology-based Formulation Strategies For Delivery Of Disulfirammentioning

confidence: 99%

Recent Advances in Repurposing Disulfiram and Disulfiram Derivatives as Copper-Dependent Anticancer Agents

Kannappan

Ali

Small

et al. 2021

Front. Mol. Biosci.

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“…CIC (0.01%) and lecithin as lipidic surfactant (0.5%w/w) were completely dissolved in liquid lipid (miglyol or labrafac at 1 or 3%) then added to molten solid lipid to form the lipid phase. At the same time, the aqueous surfactant phase of Tween 80 (2%w/w) in deionized water was preheated to the lipid temperature to avoid its recrystallization (Singh et al., 2019 ) and added drop wise to the lipid phase under thermostatic continuous stirring at 600 rpm (Banerjee et al., 2019 ) for 30 min. The resultant primary emulsion was further homogenized using an Ultra-Turrax T25 (IKA Labortechnik, Staufen im Breisgau, Germany) applying increasing intensities of 10,000 and 20,000 rpm for 5 min (Severino et al., 2012 ).…”

Section: Methodsmentioning

confidence: 99%

Enhanced alveo pulmonary deposition of nebulized ciclesonide for attenuating airways inflammations: a strategy to overcome metered dose inhaler drawbacks

et al. 2021

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Ciclesonide (CIC), an inhaled corticosteroid for bronchial asthma is currently available as metered dose inhaler (CIC-MDI) which possesses a major challenge in the management of the elderly, critically ill patients and children. In this work, nebulized CIC nano-structure lipid particles (CIC-NLPs) were prepared and evaluated for their deep pulmonary delivery and cytotoxicity to provide additional clinical benefits to patients in controlled manner and lower dose. The bio-efficacy following nebulization in ovalbumin (OVA) induced asthma Balb/c mice compared to commercial (CIC-MDI) was also assessed. The developed NLPs of 222.6 nm successfully entrapped CIC (entrapment efficiency 93.3%) and exhibited favorable aerosolization efficiency (mass median aerodynamic diameter (MMAD) 2.03 lm and fine particle fraction (FPF) of 84.51%) at lower impactor stages indicating deep lung deposition without imparting any cytotoxic effect up to a concentration of 100 lg/ml. The nebulization of 40 mg dose of the developed CIC-NLPs revealed significant therapeutic impact in the mitigation of the allergic airways inflammations when compared to 80 mg dose of the commercial CIC-MDI inhaler (Alvesco V R ). Superior anti-inflammatory and antioxidative stress effects characterized by significant decrease (p< .0001) in inflammatory cytokines IL-4 and 13, serum IgE levels, malondialdehyde (MDA), nitric oxide (NO), TNF-a, and activated nuclear factor-jB (NF-jB) activity were obvious with concomitant increase in superoxide dismutase (SOD) activity. Histological examination with inhibition of inflammatory cell infiltration in the respiratory tract was correlated well with observed biochemical improvement.

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“…In vitro cytotoxicity assessment The cytotoxicity study of free MTX, MTX encapsulated NLC (MTX-NLC) on breast cancer cell line (MCF7) was evaluated using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay [34]. Absorbance of the treated cells Cell viability (%)…”

Section: In Vitro Investigationsmentioning

confidence: 99%

Fabrication, Characterization, and in Vitro Evaluation of Pegylated Glyceride Labrasol® Nanostructured Lipid Carrier Composites of Methotrexate: The Pathway to Effective Cancer Therapy

Panda

Kuotsu

2019

Asian J Pharm Clin Res

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Objective: The objective of the current study is to optimize and evaluate the potential of polyethylene glycolylated (PEG) glyceride Labrasol® nanostructured lipid carrier (NLC) composites of methotrexate (MTX) to achieve enhanced sustained release delivery in cancer treatment. Materials and Methods: MTX-NLC was successfully prepared by hot melt emulsification and probe sonication method for spatial and controlled release of this therapeutic agent. Results: The solubility screening of MTX and lipids resulted in the selection of Monostearin as solid lipid, PEGylated glyceride Labrasol® and olive oil as liquid lipids for the formulation of MTX-loaded NLC composites. Particle size, zeta potential, and polydispersity index of both the composites were confirmed using dynamic light scattering, whereby Labrasol® MTX-NLC showed high entrapment efficiency and drug loading. A spherical particle shape with smooth surface of all the composites was confirmed from the scanning electron microscope and transmission electron microscopy analysis. Labrasol® MTX-NLC showed remarkably increased cytotoxic response, augmented cellular uptake, and low half maximal inhibitory concentration value in MCF-7 cells. In vitro release study confirmed that encapsulation of MTX in PEGylated glyceride Labrasol® MTX-NLC resulted in enhanced sustained release of MTX for a period of 48 h. Conclusion: The present study establishes that PEGylated glyceride Labrasol® MTX-NLC can be considered as a promising anticancer delivery system, thereby improving antitumor efficacy of the drug.

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Integrating the drug, disulfiram into the vitamin E-TPGS-modified PEGylated nanostructured lipid carriers to synergize its repurposing for anti-cancer therapy of solid tumors

Cited by 42 publications

References 96 publications

Recent Advances in Repurposing Disulfiram and Disulfiram Derivatives as Copper-Dependent Anticancer Agents

Recent Advances in Repurposing Disulfiram and Disulfiram Derivatives as Copper-Dependent Anticancer Agents

Enhanced alveo pulmonary deposition of nebulized ciclesonide for attenuating airways inflammations: a strategy to overcome metered dose inhaler drawbacks

Fabrication, Characterization, and in Vitro Evaluation of Pegylated Glyceride Labrasol® Nanostructured Lipid Carrier Composites of Methotrexate: The Pathway to Effective Cancer Therapy

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