Enhanced antitumor activity of epigallocatechin gallate–conjugated dual-drug-loaded polystyrene–polysoyaoil–diethanol amine nanoparticles for breast cancer therapy

2017 ◽  
Vol 33 (1) ◽  
pp. 38-62 ◽  
Author(s):  
Zeynep Karahaliloğlu ◽  
Ebru Kilicay ◽  
Pınar Alpaslan ◽  
Baki Hazer ◽  
Emir Baki Denkbas
Keyword(s):  
Breast Cancer ◽  
Release Kinetics ◽  
Epigallocatechin Gallate ◽  
Metastatic Breast ◽  
In Vitro Cytotoxicity ◽  
Single Drug ◽  
Cytotoxicity Studies ◽  
Tocopheryl Succinate ◽  
Dual Drug

The development of novel combination anticancer drug delivery systems is an important step to improve the effectiveness of anticancer treatment in metastatic breast cancer and to overcome increased toxicity of the currently used combination treatments. The aim of this study was to assess efficient targeting, therapeutic efficacy, and bioavailability of a combination of drugs (curcumin and α-tocopheryl succinate) loaded polystyrene–polysoyaoil–diethanol amine nanoparticles. Polystyrene–polysoyaoil–diethanol amine nanoparticles encapsulating two drugs, individually or in combination, were prepared by double-emulsion solvent evaporation method, resulting in particle size smaller than 250 nm with a surface negative charge between −30 and −40 mV. Entrapment efficiency of curcumin and α-tocopheryl succinate in the epigallocatechin gallate–conjugated dual-drug-loaded nanoparticles was found to be 68% and 80%, respectively. The release kinetics of curcumin and α-tocopheryl succinate from the nanoparticles exhibited a gradual and continuous profile followed by an initial burst behavior with a release over 20 days in vitro. Next, we have investigated the anticancer activity of nanoparticles encapsulating both the drugs and individually drug in human breast cancer cells (MDA-MB-231) using double-staining-based cell death analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assessment of cytotoxicity and flow cytometer. In vitro cytotoxicity studies revealed that epigallocatechin gallate–α-tocopheryl succinate/curcumin–polystyrene–polysoyaoil–diethanol amine nanoparticles are more potent than the corresponding α-tocopheryl succinate/curcumin–polystyrene–polysoyaoil–diethanol amine nanoparticles and their single-drug-loaded forms and show a synergistic and breast tumor targeting function. Thus, here, we propose epigallocatechin gallate–conjugated curcumin and α-tocopheryl succinate–loaded polystyrene–polysoyaoil–diethanol amine nanoparticles which effectively inhibit tumor growth and reduce toxicity compared to single-drug chemotherapy.

Co-loading of an anthracycline analogue Pirarubicin and Salinomycin in a 1:3 ratio into Quatramerbiodegradable polymeric nanoparticles synergistically inhibit growth of triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15047-e15047
Author(s):  
Surender Kharbanda ◽  
Anees Mohammad ◽  
Sachchidanand Tiwari ◽  
Neha Mehrotra ◽  
Sireesh Appajosyula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancers ◽  
Mice Model ◽  
Single Drug ◽  
Tnbc Cell ◽  
Dual Drug

e15047 Background: Triple negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers and differ from other types of invasive breast cancers in that they grow and spread faster. TNBCs have limited treatment options and a worse prognosis. Therapy with anthracyclines considered to be one of the most effective agents in the treatment. Unfortunately, resistance to anthracycline therapy is very common due to drug efflux mediated by overexpression of ABC transporter. Pirarubicin (PIRA), an analogue of doxorubicin (DOX), is approved in Japan, Korea and China and is shown to be less cardiotoxic than DOX. Recent studies suggest that cancer stem cells (CSCs) play an important role in tumorigenesis and biology of TNBC. Targeting CSCs may be a promising, novel strategy for the treatment of this aggressive disease. Recent studies have shown that salinomycin (SAL) preferentially targets the viability of CSCs. Methods: SAL and PIRA were co-encapsulated in polylactic acid (PLA)-based block copolymeric nanoparticles (NPs) to efficiently co-deliver these agents to treat TNBC cells. Results: Generated SAL-PIRA co-encapsulated dual drug-loaded NPs showed an average diameter of 110 ± 7 nm, zeta potential of -12.5 mV and PDI of less than 0.25. Both of these anti-cancer agents showed slow and sustained release profile in non-physiological buffer (PBS, pH 7.4) from these dual drug-encapsulated NPs. Additionally, multiple ratios (PIRA:SAL = 3:1, 1:1, 1:3) were encapsulated to generate diverse dual drug-loaded NPs. The results demonstrate that, in contrast to 1:1 and 3:1, treatment of TNBC cells with 1:3 ratio of PIRA:SAL dual drug-loaded NPs, was associated with significant inhibition of growth in vitro in multiple TNBC cell lines. Interestingly, PIRA:SAL (1:3) was synergistic as compared to either SAL- or PIRA single drug-loaded NPs. The IC50 of PIRA and SAL in single drug-encapsulated NPs is 150 nM and 700 nM respectively in MDA-MB-468. Importantly, the IC50 of PIRA in dual drug-encapsulated NPs dropped down to 30 nM (5-fold). Similar results were obtained in SUM-149 TNBC cell line. Studies are underway to evaluate in vivo biological activity of PIRA:SAL (1:3) on tumor growth in a TNBC xenograft mice model. Conclusions: These results demonstrate that a novel dual drug-loaded NP formulation of PIRA and SAL in a unique ratio of 1:3 represents an approach for successful targeting of CSCs and bulk tumor cells in TNBC and potentially other cancer types.

scholarly journals Development, Characterization and In Vitro Evaluation of Paclitaxel and Anastrozole Co-Loaded Liposome

Processes ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1110
Author(s):  
Minh Thanh Vu ◽  
Dinh Tien Dung Nguyen ◽  
Ngoc Hoi Nguyen ◽  
Van Thu Le ◽  
The Nam Dao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Combination Therapy ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Breast Cancer Treatment ◽  
In Vitro Cytotoxicity ◽  
Cytotoxicity Studies ◽  
Combined Drugs

Paclitaxel (PTX) and anastrozole (ANA) have been frequently applied in breast cancer treatment. PTX is well-known for its anti-proliferative effect meanwhile ANA has just been discovered to act as an estrogen receptor α (ERα) ligand. The combination therapy of PTX and ANA is expected to improve treating efficiency, as ANA would act as a ligand binding with the ERα gene expressed in breast cancer cells and thereafter PTX would inhibit the division and cause death to those cancer cells. In this study, liposome-based nanocarriers (LP) were developed for co-encapsulation of PTX and ANA to improve the efficacy of the combined drugs in an Estrogen receptor-responsive breast cancer study. PTX-ANA co-loaded LP was prepared using thin lipid film hydration method and was characterized for morphology, size, zeta potential, drug encapsulation and in vitro drug release. In addition, cell proliferation (WST assay) and IN Cell Analyzer were used for in vitro cytotoxicity studies on a human breast cancer cell line (MCF-7). Results showed that the prepared LP and PTX-ANA-LP had spherical vesicles, with a mean particle size of 170.1 ± 13.5 nm and 189.0 ± 22.1 nm, respectively. Controlled and sustained releases were achieved at 72 h for both of the loaded drugs. The in vitro cytotoxicity study found that the combined drugs showed higher toxicity than each single drug separately. These results suggested a new approach to breast cancer treatment, consisting of the combination therapy of PTX and ANA in liposomes based on ER response.

scholarly journals IN VITRO-CYTOTOXICITY STUDIES OF METHANOLIC LEAF EXTRACT OF MEMOCYLON UMBELLATUM BURM.F. AGAINST BREAST CANCER.

2017 ◽  
Vol 5 (12) ◽  
pp. 1980-1984
Author(s):  
VikramR Palled ◽  
◽  
Badarinath Kulkarni ◽  
Harish Handral ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Leaf Extract ◽  
In Vitro Cytotoxicity ◽  
Cytotoxicity Studies

Formulation and Optimization of Paclitaxel Loaded Lipid Nanoparticles and Their In Vitro Cytotoxicity Studies Using H1299 Lung Cancer Cell Lines

2019 ◽  
Vol 11 (12) ◽  
pp. 1202-1217 ◽  
Author(s):  
Hiren Khatri ◽  
Nimitt Chokshi ◽  
Shruti Rawal ◽  
Bhoomika Patel ◽  
Mayur M. Patel
Keyword(s):  
Lung Cancer ◽  
Particle Size ◽  
Cell Lines ◽  
Release Kinetics ◽  
Drug Loading ◽  
Lipid Nanoparticles ◽  
In Vitro Cytotoxicity ◽  
H1299 Cell ◽  
Cytotoxicity Studies

Lung cancer is the leading cause of cancer-related death in the world, and approximately 80% to 85% of lung cancers are non-small cell lung cancer (NSCLC). Paclitaxel (PTX) has been widely used for the treatment of NSCLC. It is classified as a BCS class IV drug and offers a low therapeutic index. The present investigation demonstrates development of orally administered PEGylated, PTX loaded solid lipid nanoparticles (PTX-SLNs). A Box-Behnken design was applied to systematically optimize PTX-SLNs. Drug concentration, emulsifier concentration and homogenization pressure were selected as an independent variables, and particle size, % entrapment efficiency (%EE) and % drug loading (%DL) were selected as dependent variables. The particle size of optimized PTXSLNs was found to be 401 ± 12 nm, with %EE of 86.63 ± 2.58%, and %DL of 7.42 ± 0.11%. The developed PTX-SLNs exhibited anti-lipolytic effect due to its stabilization by MPEG2000-DSPE. Moreover, the in vitro GI stability studies revealed good stability of PTX-SLNs in various GI tract media. The in vitro drug release studies revealed controlled release profile with Weibull model release kinetics. In vitro cytotoxicity studies in H1299 cell lines revealed significant decline in IC50 values of PTX-SLNs treated cells as compared to pure drug, thus revealing an improved efficacy of the developed systems.

A comparative study of the photophysicochemical and photodynamic activity properties of meso-4-methylthiophenyl functionalized Sn(IV) tetraarylporphyrins and triarylcorroles

2020 ◽  
Vol 24 (09) ◽  
pp. 1138-1145
Author(s):  
Somila Dingiswayo ◽  
Balaji Babu ◽  
Earl Prinsloo ◽  
John Mack ◽  
Tebello Nyokong
Keyword(s):  
Breast Cancer ◽  
Cellular Uptake ◽  
Breast Cancer Cells ◽  
Molar Absorptivity ◽  
In Vitro Cytotoxicity ◽  
Cytotoxicity Studies ◽  
Photodynamic Activity ◽  
Irradiation Wavelength ◽  
Mcf 7

Tin(IV) complexes of a 4-methylthiophenyl functionalized porphyrin (1-Sn) and its corrole analogue (2-Sn) were synthesized so that their photophysicochemical properties and photodynamic activities against MCF-7 breast cancer cells could be compared. Singlet oxygen luminescence studies revealed that 1-Sn and 2-Sn have comparable [Formula: see text] values in DMF of 0.59 and 0.60, respectively, while the IC[Formula: see text] values after irradiation of MCF-7 cells for 30 min with a Thorlabs 625 nm LED (432 J · cm[Formula: see text] were determined to be 12.4 and 8.9 [Formula: see text]M. The results demonstrate that the cellular uptake of 2-Sn and its molar absorptivity at the irradiation wavelength play a crucial role during in vitro cytotoxicity studies.

scholarly journals Comparative Analysis of Pentacyclic Triterpenic Acid Compositions in Oleogum Resins of Different Boswellia Species and Their In Vitro Cytotoxicity against Treatment-Resistant Human Breast Cancer Cells

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2153 ◽  
Author(s):  
Michael Schmiech ◽  
Sophia J. Lang ◽  
Katharina Werner ◽  
Luay J. Rashan ◽  
Tatiana Syrovets ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Comparative Analysis ◽  
Cancer Cells ◽  
High Performance ◽  
Metastatic Breast ◽  
Cancer Cell Line ◽  
In Vitro Cytotoxicity ◽  
Treatment Resistant ◽  
Triterpenic Acids

Pentacyclic triterpenic acids from oleogum resins of Boswellia species are of considerable therapeutic interest. Yet, their pharmaceutical development is hampered by uncertainties regarding botanical identification and the complexity of triterpenic acid mixtures. Here, a highly sensitive, selective, and accurate method for the simultaneous quantification of eight boswellic and lupeolic acids by high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS) was developed. The method was applied to the comparative analysis of 41 oleogum resins of the species B. sacra, B. dalzielli, B. papyrifera, B. serrata, B. carterii, B. neglecta, B. rivae, B. frereana, and B. occulta. Multivariate statistical analysis of the data revealed differences in the triterpenic acid composition that could be assigned to distinct Boswellia species and to their geographic growth location. Extracts of the oleogum resins exhibited cytotoxicity against the human, treatment-resistant, metastatic breast cancer cell line MDA-MB-231. Extracts from B. sacra were the most potent ones with an average IC50 of 8.3 ± 0.6 µg/mL. The oleogum resin of the B. sacra was further fractionated to enrich different groups of substances. The cytotoxic efficacy against the cancer cells correlates positively with the contents of pentacyclic triterpenic acids in Boswellia extracts.

scholarly journals Development and Characterization of Soy Lecithin Liposome as Potential Drug Carrier Systems for Codelivery of Letrozole and Paclitaxel

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Minh Thanh Vu ◽  
Ngoc Thuy Trang Le ◽  
Truc Le-Buu Pham ◽  
Ngoc Hoi Nguyen ◽  
Dai Hai Nguyen
Keyword(s):  
Breast Cancer ◽  
Drug Carrier ◽  
Diffusion Mechanism ◽  
Cancer Cell Line ◽  
In Vitro Cytotoxicity ◽  
Soy Lecithin ◽  
Liposomal System ◽  
Thin Film Layer ◽  
Dual Drug

In the present work, a dual-drug-loaded soy lecithin liposomal system was developed by coencapsulation of Letrozole (LET) with Paclitaxel (PTX) to improve the efficacy in breast cancer therapy. Liposomes were synthesized by the thin film layer hydration. To sufficiently evaluate the characteristics of these liposomes, the particle size, zeta potential, morphology, drug encapsulation, in vitro drug release, and cytotoxicity were ascertained. Results showed promisingly anticancer potentials, as the following parameters indicated: nanosize diameter (around 193 nm) and negative surface charge. Data collected from the coloaded drug liposomes showed suitable encapsulation efficiency (50.56% for PTX and 31.13% for LET). Controlled and sustained releases were achieved up to 72 h for both the loaded drugs following the diffusion mechanism. In addition, the in vitro cytotoxicity study on the human breast cancer cell line (MCF-7) given the dual-drug-loaded liposome showed greater inhibition of cell growth than the single drug. Consequently, LET and PTX coloaded liposomes made from soy lecithin are expected to be an ingenious drug-delivery system for combination chemotherapy.

Anticancer Potential of Aguerin B, a Sesquiterpene Lactone Isolated from Centaurea behen in Metastatic Breast Cancer Cells

2020 ◽  
Vol 15 (2) ◽  
pp. 165-173
Author(s):  
Elaheh Amini ◽  
Mohammad Nabiuni ◽  
Seyed Bahram Behzad ◽  
Danial Seyfi ◽  
Farhad Eisvand ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Tumor Cell ◽  
Sesquiterpene Lactone ◽  
Sesquiterpene Lactones ◽  
Metastatic Breast ◽  
Breast Adenocarcinoma ◽  
Human Breast ◽  
Skin Malignancy

Background: Breast carcinoma is a malignant disease that represents the most common non-skin malignancy and a chief reason of cancer death in women. Large interest is growing in the use of natural products for cancer treatment, especially with goal of suppression angiogenesis, tumor cell growth, motility, as well as invasion and metastasis with low/no toxicity. It is evident from recent patents on the anticancer properties of sesquiterpene lactones such as parthenolide. Objective: In this study, using MDA-MB-231 cells of a human breast adenocarcinoma, the effects of aguerin B, as a natural sesquiterpene lactone, has been evaluated, in terms of the expression of metastatic-related genes (Pak-1, Rac-1 and HIF-1α). Methods: Cytotoxicity of aguerin B was tested toward MDA-MB-231 breast tumor cells using MTT. Scratch assay was accomplished to evaluate the tumor cell invasion. To understand the underlying molecular basis, the mRNA expressions were evaluated by real time PCR. Results: It was found that aguerin B significantly inhibited human breast cancer cell growth in vitro (IC50 = 2μg/mL) and this effect was accompanied with a persuasive suppression on metastasis. Our results showed that aguerin B in IC50 concentration down-regulated Rac-1, Pak-1, Hif-1α and Zeb-1 transcriptional levels. Conclusion: Taken together, this study demonstrated that aguerin B possessed potential anti-metastatic effect, suggesting that it may consider as a potential multi target bio compound for treatment of breast metastatic carcinoma.

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