In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

Thymopentin, a potent immunomodulating drug, was incorporated into pH-sensitive chitosan nanoparticles prepared by ionic gelation of chitosan with tripolyphosphate anions and then coated with Eudragit S100 to improve the stability and the oral bioavailability. Nanoparticles particle size and zeta potential were measured by photo correction spectroscopy and laser Dopper anemometry. Its morphology was examined by environment scan electron microscope. The encapsulation efficiency and the release in vitro were determined by HPLC. Enzymatic stabilization was expressed by the enzymatic degradation of aminopeptidase. Biological activity of TP5 loaded in nanoparticles was assayed by lymphocyte proliferation test in vitro and the immune function (CD4+/CD8+) of irradiated rat in vivo. The results obtained demonstrated that the average sizes of pH-sensitive chitosan nanoparticles were 175.6 ± 17 nm, the zeta potential was 28.44 ± 0.5 mV and the encapsulation efficiency was 76.70 ± 2.6%. The cumulative release percentages of thymopentin from the pH-sensitive nanoparticles were 24.65%, 41.01%, and 81.44% incubated in different medium, 0.1 N HCl, pH 5.0 PBS, and pH 7.4 PBS, respectively. The pH-sensitive chitosan nanoparticles could efficiently protect TP5 from enzymatic degradation and prolong the degradation half-time of TP5 from 1.5 min to 15 min. It was demonstrated from the lymphocyte proliferation test that the nanoparticle-encapsulated TP5 still kept its biological activity. In immunosuppression rats, the lowered T-lymphocyte subsets values were significantly increased and the raised CD4+/CD8+ ratio was evidently reduced. These results indicated that pH-sensitive chitosan nanoparticles may be used as the vector in oral drug delivery system for TP5.

Download Full-text

Overcoming MDR by Associating Doxorubicin and pH-Sensitive PLGA Nanoparticles Containing a Novel Organoselenium Compound—An In Vitro Study

Pharmaceutics ◽

10.3390/pharmaceutics14010080 ◽

2021 ◽

Vol 14 (1) ◽

pp. 80

Author(s):

Letícia Bueno Macedo ◽

Daniele Rubert Nogueira-Librelotto ◽

Daniela Mathes ◽

Josiele Melo de Vargas ◽

Raquel Mello da Rosa ◽

...

Keyword(s):

Antitumor Activity ◽

Tumor Cells ◽

In Vitro Study ◽

Plga Nanoparticles ◽

Ph Sensitive ◽

Organoselenium Compound ◽

Cytotoxic Effects ◽

Nanoprecipitation Method ◽

Mcf 7

In this study, we developed PLGA nanoparticles (NPs) as an effective carrier for 5′-Se-(phenyl)-3-(amino)-thymidine (ACAT-Se), an organoselenium compound, nucleoside analogue that showed promising antitumor activity in vitro. The PLGA NPs were prepared by the nanoprecipitation method and modified with a pH-responsive lysine-based surfactant (77KL). The ACAT-Se-PLGA-77KL-NPs presented nanometric size (around 120 nm), polydispersity index values <0.20 and negative zeta potential values. The nanoencapsulation of ACAT-Se increased its antioxidant (DPPH and ABTS assays) and antitumor activity in MCF-7 tumor cells. Hemolysis study indicated that ACAT-Se-PLGA-77KL-NPs are hemocompatible and that 77KL provided a pH-sensitive membranolytic behavior to the NPs. The NPs did not induce cytotoxic effects on the nontumor cell line 3T3, suggesting its selectivity for the tumor cells. Moreover, the in vitro antiproliferative activity of NPs was evaluated in association with the antitumor drug doxorubicin. This combination result in synergistic effect in sensitive (MCF-7) and resistant (NCI/ADR-RES) tumor cells, being especially able to successfully sensitize the MDR cells. The obtained results suggested that the proposed ACAT-Se-loaded NPs are a promising delivery system for cancer therapy, especially associated with doxorubicin.

Download Full-text

Comparative Antitumor Activity of Jelly Ear Culinary-Medicinal Mushroom, Auricularia auricula-judae (Bull.) J. Schrot. (Higher Basidiomycetes) Extracts Against Tumor Cells In Vitro

International Journal of Medicinal Mushrooms ◽

10.1615/intjmedmushr.v14.i4.80 ◽

2012 ◽

Vol 14 (4) ◽

pp. 403-409 ◽

Cited By ~ 4

Author(s):

Md.Ahsanur Reza ◽

Woo-Sik Jo ◽

Seung-Chun Park

Keyword(s):

Antitumor Activity ◽

Tumor Cells ◽

Medicinal Mushroom ◽

Auricularia Auricula

Download Full-text

Faculty Opinions recommendation of The mTORC1 inhibitor everolimus has antitumor activity in vitro and produces tumor responses in patients with relapsed T-cell lymphoma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725453797.793521222 ◽

2016 ◽

Author(s):

Bruce Smoller

Keyword(s):

T Cell ◽

Antitumor Activity ◽

Cell Lymphoma ◽

T Cell Lymphoma

Download Full-text

Formulation of Modified Release Atorvastatin Nanoparticles by Emulsion Interfacial Reaction Method

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2015.8.3.7 ◽

2015 ◽

Vol 8 (3) ◽

pp. 2937-2940

Author(s):

Sudhakar Sekar ◽

Shee Sim May

Keyword(s):

Interfacial Reaction ◽

Therapeutic Potential ◽

Chitosan Nanoparticles ◽

In Vitro Release ◽

Morphological Characteristics ◽

Preparation Technique ◽

Modified Release ◽

Reaction Method ◽

Vitro Release

The aim of the study is to formulate a modified release chitosan nanoparticles for the oral delivery of atorvastatin and to study the in vitro release of atorvastatin from chitosan nanoparticles. Atorvastatin-loaded chitosan nanoparticles were prepared with different concentration of cross-linking agent (glutaraldehyde) by emulsion interfacial reaction method. The formed nanoparticles were characterized in terms of size and morphological characteristics by scanning electron microscopy (SEM) and transmission electron microscope (TEM). Spherical and regular nanoparticles with the size range of 100-250nm were formed. Atorvastatin encapsulation efficiency of nanoparticles was found to be highest in ANP3, followed by ANP2 and ANP1. The in vitro release of atorvastatin was studied by membrane diffusion technique. The resulted cumulative percentage of drug released for ANP1, ANP2 and ANP3 were 60.08%, 34.81% and 20.39% respectively. Through this study, the nanoparticles preparation technique has shown to be a promising approach for enhancing the dissolution of hydrophobic drugs like atorvastatin calcium. The application of this novel delivery system offers good therapeutic potential in the management of hypercholesterolemia and dyslipidemia.

Download Full-text

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

Problems in oncology ◽

10.37469/0507-3758-2019-65-5-760-765 ◽

2019 ◽

Vol 65 (5) ◽

pp. 760-765

Author(s):

Margarita Tyndyk ◽

Irina Popovich ◽

A. Malek ◽

R. Samsonov ◽

N. Germanov ◽

...

Keyword(s):

Antitumor Activity ◽

Tumor Growth ◽

Tumor Cells ◽

Human Tumor ◽

Significant Inhibition ◽

In Vivo Studies ◽

Ehrlich Carcinoma ◽

In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

Download Full-text

5-Nitro-Thiophene-Thiosemicarbazone Derivatives Present Antitumor Activity Mediated by Apoptosis and DNA Intercalation

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190621120304 ◽

2019 ◽

Vol 19 (13) ◽

pp. 1075-1091 ◽

Cited By ~ 4

Author(s):

Karla Mirella Roque Marques ◽

Maria Rodrigues do Desterro ◽

Sandrine Maria de Arruda ◽

Luiz Nascimento de Araújo Neto ◽

Maria do Carmo Alves de Lima ◽

...

Keyword(s):

Cell Cycle ◽

Antitumor Activity ◽

Cell Line ◽

Mitochondrial Membrane ◽

In Vitro Cytotoxicity ◽

Dna Intercalation ◽

Phase Cell ◽

Fluorescence Studies ◽

In Silico Studies

Background: Considering the need for the development of new antitumor drugs, associated with the great antitumor potential of thiophene and thiosemicarbazonic derivatives, in this work we promote molecular hybridization approach to synthesize new compounds with increased anticancer activity. Objective: Investigate the antitumor activity and their likely mechanisms of action of a series of N-substituted 2-(5-nitro-thiophene)-thiosemicarbazone derivatives. Methods: Methods were performed in vitro (cytotoxicity, cell cycle progression, morphological analysis, mitochondrial membrane potential evaluation and topoisomerase assay), spectroscopic (DNA interaction studies), and in silico studies (docking and molecular modelling). Results: Most of the compounds presented significant inhibitory activity; the NCIH-292 cell line was the most resistant, and the HL-60 cell line was the most sensitive. The most promising compound was LNN-05 with IC50 values ranging from 0.5 to 1.9 µg.mL-1. The in vitro studies revealed that LNN-05 was able to depolarize (dose-dependently) the mitochondrial membrane, induceG1 phase cell cycle arrest noticeably, promote morphological cell changes associated with apoptosis in chronic human myelocytic leukaemia (K-562) cells, and presented no topoisomerase II inhibition. Spectroscopic UV-vis and molecular fluorescence studies showed that LNN compounds interact with ctDNA forming supramolecular complexes. Intercalation between nitrogenous bases was revealed through KI quenching and competitive ethidium bromide assays. Docking and Molecular Dynamics suggested that 5-nitro-thiophene-thiosemicarbazone compounds interact against the larger DNA groove, and corroborating the spectroscopic results, may assume an intercalating interaction mode. Conclusion: Our findings highlight 5-nitro-thiophene-thiosemicarbazone derivatives, especially LNN-05, as a promising new class of compounds for further studies to provide new anticancer therapies.

Download Full-text

Synthesis and Antitumor Activity Evaluation of New Phenanthrene-Based Tylophorine Derivatives

Letters in Organic Chemistry ◽

10.2174/1570178615666181025115513 ◽

2019 ◽

Vol 16 (6) ◽

pp. 462-467

Author(s):

Songtao Li ◽

Hongling Zhao ◽

Zhifeng Yin ◽

Shuhua Deng ◽

Yang Gao ◽

...

Keyword(s):

Antitumor Activity ◽

Cell Lines ◽

Antitumor Activities ◽

Human Carcinoma ◽

Carcinoma Cell Lines ◽

Structure Activity ◽

Human Carcinoma Cell ◽

Ic50 Values ◽

Relationship Of

A series of new phenanthrene-based tylophorine derivatives (PBTs) were synthesized in good yield and their structures were characterized by 1H-NMR spectroscopy and ESI MS. In vitro antitumor activity of these compounds against five human carcinoma cell lines, including HCT116 (colorectal), BGC-823 (gastric), HepG-2 (hepatic), Hela (cervical) and H460 (lung) cells, was evaluated by MTT assay. Among these PBTs, compound 6b showed the highest antitumor activities against HCT116 and HepG-2 cell lines with IC50 values of 6.1 and 6.4 μM, respectively, which were comparable to that of adriamycin hydrochloride. The structure-activity relationship of these compounds was also discussed based on the results of their antitumor activity.

Download Full-text

Improved Method for Obtaining of Arctigenin from Arctium Lappa L. and its Antiproliferative Effect on Human Hepatocarcinoma HepG2 Cells

Current Bioactive Compounds ◽

10.2174/1573407214666181115124223 ◽

2020 ◽

Vol 16 (3) ◽

pp. 358-362

Author(s):

Renan S. Teixeira ◽

Paulo H.D. Carvalho ◽

Jair A.K. Aguiar ◽

Valquíria P. Medeiros ◽

Ademar A. Da Silva Filho ◽

...

Keyword(s):

Antitumor Activity ◽

Crude Extract ◽

Hepg2 Cells ◽

Liver Carcinoma ◽

Adhesion Assay ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Arctium Lappa ◽

Nih 3T3

Background: Arctigenin is a lignan found in Arctium lappa L. (Asteraceae) that displays anti-inflammatory activities. Previous studies showed that the crude extract of A. Lappa has antitumor activity in human liver carcinoma, lung and stomach cancer cells. The aim of this study was to obtain arctigenin from A. lappa L., as well as to evaluate its antiproliferative effects in cells of liver carcinoma (HepG2) and fibroblasts (NIH/3T3). Methods: Arctigenin was obtained from the hydrolysis of arctiin, which was isolated from the crude extract of A. lappa. The effects of arctigenin and arctiin on HepG2 cell viability and cell adhesion were analyzed by MTT method. Adhesion assay was also carried out to evaluate the antitumor activity. Results: Our results showed that the analytical process to obtain arctigenin was fast and easy. In vitro experiments showed that arctigenin (107-269 μM) decreased HepG2 cells viability and did not cause cytotoxicity on NIH/3T3 cells. Arctigenin (27-269 μM) demonstrated anti-adhesion in HepG2 cells in a concentration-dependent manner, when compared with control. Conclusion: These results suggest a promising pharmacological activity for arctigenin as an antiproliferative compound.

Download Full-text