Metformin and Silibinin co-loaded PLGA-PEG nanoparticles for effective combination therapy against human breast cancer cells

Amirsaadat, Soumaye; Jafari-Gharabaghlou, Davoud; Alijani, Sepideh; Mousazadeh, Hanieh; Dadashpour, Mehdi

doi:10.1016/j.jddst.2020.102107

Cited by 36 publications

(14 citation statements)

References 42 publications

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“…Various studies in consistent with our study have shown that free MET and MET-NPs as well as in combined with other chemotherapeutic molecules can alter the expression levels of apoptosis genes (16,21). In the preliminary study conducted in our group, it was found that MET in combination with SIL exhibits synergistic antiproliferative effects via down-regulating Cyclin D1 and hTERT (16). Moreover, in another study conducted by our group, it was shown that MET loaded into polymeric PLGA-PEG NPs may be a convenient drug delivery system to enhance its anticancer effects for ovarian cancer therapy (9).…”

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 86%

“…In one study, the effect of MET-NPs showed a greater inhibitory effect than pure MET by reducing the expression of the hTERT gene in T47D and MDA-MB-231 cell lines in in vitro [16]. Liou and co-colleges showed that MET and SIL in combination form prevent the survival of human cervical cancer cells (17).…”

Section: Discussionmentioning

confidence: 99%

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Metformin-Loaded Nanostructured Plga: A New Strategy for Enhancing Efficacy of Metformin in Breast Cancer Treatment

Dadashpour¹,

Yaghoutrang²,

Zarghami³

et al. 2020

EJOH

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Objective: Nano-formulation approaches would be more efficient in decreasing drug toxicity, preventing tumor development in relation to free form of drug.Methods: Therefore, the purpose of this study is to construct poly lactic-coglycolic acid (PLGA) nanoparticles (NPs) loaded with Metformin (MET) to investigate their cytotoxicity as well as their impact on expression levels of apoptosis related genes in MDA-MB-231 breast cancer cells. Field Emission Scanning Electron Microscope (FE-SEM) and Fourier-transform infrared spectroscopy (FTIR) characterized the synthesized NPs. Then, MTT assay was used to evaluate and compare the cytotoxic effect of various concentrations of the chemotherapeutic molecules in pure and nano-formulated forms after 48 h exposure time. Moreover, the mRNA levels of apoptosis related genes expression were studied by quantitative PCR.Results: By encapsulating MET into PLGA, the cytotoxic efficiency of the compounds considerably augmented for all concentrations. Furthermore, the results demonstrated that MET-loaded NPs could induce apoptosis in MDA-MB-231 breast cancer cell by upregulation of caspase-3, caspase-7 and BAX, along with Bcl-XL, hTERT and Cyclin D1 down regulation.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 86%

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Metformin-Loaded Nanostructured Plga: A New Strategy for Enhancing Efficacy of Metformin in Breast Cancer Treatment

Dadashpour¹,

Yaghoutrang²,

Zarghami³

et al. 2020

EJOH

Self Cite

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“…Worldwide, breast cancer is one of the most common cancers among women and the leading cause of death after lung cancer. The prognosis of this cancer is about five years in 75% of women [1]. Chemotherapy and radiation therapies are commonly used treatment modules for this type of cancer.…”

Section: Introductionmentioning

confidence: 99%

Formulation of Genistein-HP β Cyclodextrin-Poloxamer 188 Ternary Inclusion Complex: Solubility to Cytotoxicity Assessment

et al. 2021

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The current study was designed to prepare the inclusion complex Genistein (GS) using Hydroxypropyl β cyclodextrin (HP β CD) and poloxamer 188 (PL 188). The binary inclusion complex (GS BC) and ternary inclusion complex (GS TC) were developed by microwave irradiation technique and evaluated for a comparative dissolution study. Further, the samples were assessed for FTIR, DSC, XRD, and NMR for the confirmation of complex formation. Finally, antioxidant and antimicrobial studies and cytotoxicity studies on a breast cancer (MCF-7) cell line were conducted. The dissolution study result showed a marked increment in GS dissolution/release after incorporation in binary (GS: HP β CD, 1:1) and ternary (GS: HP β CD: PL 188; 1:1:0.5) inclusion complexes. Moreover, the ternary complex exhibited a significant enhancement (p < 0.05) in dissolution than did the binary complexes. This might be due to the presence of PL 188, which helps in solubility enhancement of GS. DSC, XRD and SEM evaluation confirmed the modification in the structure of GS. FTIR and NMR results indicated the formation of an inclusion complex. The antioxidant and antimicrobial activity results revealed that GS TC has shown significant (p < 0.05) higher activity than pure GS. The cytotoxicity study results also depicted concentration-dependent cytotoxicity. GS TC exhibited significantly (p < 0.05) high cytotoxicity to cancer cells (IC50 = 225 µg/mL) than pure GS (IC50 = 480 µg/mL). Finally, it was concluded that a remarkable enhancement in the dissolution was observed after the inclusion of GS in the ternary complex and it therefore has significant potential for the treatment of breast cancer.

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“…To overcome these limitations and to mitigate the unfavorable pharmacokinetic profile, different nanoparticle-based drug delivery approaches are being developed to improve SBN bioavailability [15,16]. Systems based on polymeric nanoparticles demonstrate long-term stability, improved effectiveness, non-toxicity, and targeted drug release in comparison with traditional carriers [17][18][19][20]. In addition, when the particle size is under 200 nm, an increased drug accumulation in tumor cells is observed due to enhanced permeability [21].…”

Section: Introductionmentioning

confidence: 99%

PEG-Modified tert-Octylcalix[8]arenes as Drug Delivery Nanocarriers of Silibinin

et al. 2021

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The hepatoprotective properties of silibinin, as well its therapeutic potential as an anticancer and chemo-preventive agent, have failed to progress towards clinical development and commercialization due to this material’s unfavorable pharmacokinetics and physicochemical properties, low aqueous solubility, and chemical instability. The present contribution is focused on the feasibility of using PEGylated calixarene, in particular polyoxyethylene-derivatized tert-octylcalix[8]arene, to prepare various platforms for the delivery of silibinin, such as inclusion complexes and supramolecular aggregates thereof. The inclusion complex is characterized by various instrumental methods. At concentrations exceeding the critical micellization concentration of PEGylated calixarene, the tremendous solubility increment of silibinin is attributed to the additional solubilization and hydrophobic non-covalent interactions of the drug with supramolecular aggregates. PEG-modified tert-octylcalix[8]arenes, used as drug delivery carriers for silibinin, were additionally investigated for cytotoxicity against human tumor cell lines.

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Metformin and Silibinin co-loaded PLGA-PEG nanoparticles for effective combination therapy against human breast cancer cells

Cited by 36 publications

References 42 publications

Metformin-Loaded Nanostructured Plga: A New Strategy for Enhancing Efficacy of Metformin in Breast Cancer Treatment

Metformin-Loaded Nanostructured Plga: A New Strategy for Enhancing Efficacy of Metformin in Breast Cancer Treatment

Formulation of Genistein-HP β Cyclodextrin-Poloxamer 188 Ternary Inclusion Complex: Solubility to Cytotoxicity Assessment

PEG-Modified tert-Octylcalix[8]arenes as Drug Delivery Nanocarriers of Silibinin

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