Evaluation of Paclitaxel Nanocrystals In Vitro and In Vivo

Drug Research ◽  
2017 ◽  
Vol 68 (04) ◽  
pp. 205-212 ◽  
Author(s):  
Wanqing Li ◽  
Zhiguo Li ◽  
Lisha Wei ◽  
Aiping Zheng
Keyword(s):  
Drug Concentration ◽  
Antitumor Effects ◽  
High Drug ◽  
High Drug Concentration ◽  
Low Toxicity ◽  
Nanoparticle Drug Delivery ◽  
Antitumor Evaluation ◽  
Mcf 7

AbstractWe created a novel paclitaxel (PTX) nanoparticle drug delivery system and compared this to acommercial injection preparation to evaluate the antitumor effects for both formulations in vivo and in vitro.PTXnanocrystals were 194.9 nm with potential of −29.6 mV. Cytotoxicity tests indicated that both formulations had similar effects and cytotoxicity was dose- and time-dependent.Pharmacodynamics indicated that the drug concentration at the tumor was greater with PTX nanocrystals compared to commercial injection (P<0.01) and that drug accumulated more and for a longer duration. In vivo antitumor evaluation indicated significant antitumor effects and low toxicity of PTX nanocrystals. Moreover, bioimaging indicated that the PTX retention time in MCF-7-bearing mice was longer, especially at the tumor site, and this high drug concentration was maintained for a long time.Overall, PTX nanocrystalsare feasible and superior to traditional injection formulation chemotherapy.

In vitro evaluation of estrogenic, antiestrogenic and antitumor effects of amentoflavone

2021 ◽  
pp. 096032712199945
Author(s):  
AT Aliyev ◽  
S Ozcan-Sezer ◽  
A Akdemir ◽  
H Gurer-Orhan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Effects ◽  
Antiestrogenic Activity ◽  
Er Positive ◽  
In Vivo Effects ◽  
Mcf 7

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.

scholarly journals Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1260
Author(s):  
Waiting Tai ◽  
Michael Yee Tak Chow ◽  
Rachel Yoon Kyung Chang ◽  
Patricia Tang ◽  
Igor Gonda ◽  
...  
Keyword(s):  
Drug Concentration ◽  
Systemic Exposure ◽  
Oral Route ◽  
Liquid Volume ◽  
Global Public Health ◽  
Promising Alternative ◽  
High Drug Concentration ◽  
Preclinical And Clinical Studies

The coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has severely impacted global public health and the economy. Hydroxychloroquine administered orally to COVID-19 patients was ineffective, but its antiviral and anti-inflammatory actions were observed in vitro. The lack of efficacy in vivo could be due to the inefficiency of the oral route in attaining high drug concentration in the lungs. Delivering hydroxychloroquine by inhalation may be a promising alternative for direct targeting with minimal systemic exposure. This paper reports on the characterisation of isotonic, pH-neutral hydroxychloroquine sulphate (HCQS) solutions for nebulisation for COVID-19. They can be prepared, sterilised, and nebulised for testing as an investigational new drug for treating this infection. The 20, 50, and 100 mg/mL HCQS solutions were stable for at least 15 days without refrigeration when stored in darkness. They were atomised from Aerogen Solo Ultra vibrating mesh nebulisers (1 mL of each of the three concentrations and, in addition, 1.5 mL of 100 mg/mL) to form droplets having a median volumetric diameter of 4.3–5.2 µm, with about 50–60% of the aerosol by volume < 5 µm. The aerosol droplet size decreased (from 4.95 to 4.34 µm) with increasing drug concentration (from 20 to 100 mg/mL). As the drug concentration and liquid volume increased, the nebulisation duration increased from 3 to 11 min. The emitted doses ranged from 9.1 to 75.9 mg, depending on the concentration and volume nebulised. The HCQS solutions appear suitable for preclinical and clinical studies for potential COVID-19 treatment.

scholarly journals Fruticuline A, a chemically-defined diterpene, exerts antineoplastic effects in vitro and in vivo by multiple mechanisms

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Claudia Rita Corso ◽  
Maria Carolina Stipp ◽  
Débora Rasec Radulski ◽  
Marihá Mariott ◽  
Luisa Mota da Silva ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Molecular Mechanisms ◽  
Tumor Tissue ◽  
Human Cancer ◽  
Biological Properties ◽  
Ehrlich Carcinoma ◽  
Antitumor Effects ◽  
Mcf 7

Abstract Natural products have been recognized as important bioactive compounds on the basis of their wide biological properties. Here we investigated the antitumor effect and molecular mechanisms of the diterpene Fruticuline A (fruti) from Salvia lachnostachys, in human cancer cell lineages and Solid Ehrlich Carcinoma in mice. Fruti reduced MCF-7 and HepG2 proliferation by the reduction of Cyclin D1 levels and decreased NF-κB gene levels in both cell types. Furthermore, fruti also induced apoptosis in HepG2 cells, reduced Bcl-2 gene expression and induced necroptosis by increasing Ripk in MCF-7 cells. In mice, fruti prevented tumor development and reduced Cyclin D1, Bcl-2 and Rela gene levels, and reduced the p-NF-κB/NF-κB ratio in tumor tissue. Furthermore, fruti induced necrosis and apoptosis, increased N-acetyl-β-D-glucosaminidase and TNF-α levels and reduced IL-10 and Vegf levels in tumor tissue. Collectively, fruti exerts antitumor effects through the inhibition of the NF-κB pathway, reducing Cyclin D1 and Bcl-2 levels. In vitro the apoptosis and necroptosis pathways are involved in the cellular death, whereas in vivo, cells undergo necrosis by increased tumor inflammation and reduction of angiogenesis. Thus, fruticuline A acts in tumor cells by multiple mechanisms and represents a promising molecule for drug development in cancer treatment.

New targeted anti CDK4/6 peptide MM-D37K.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13545-e13545 ◽  
Author(s):  
Vladimir Konstantinovich Bozhenko ◽  
Tatyana Michailovna Kulinich ◽  
Elena Aleksandrovna Kudinova ◽  
Andrey Boldyrev ◽  
Vladimir Alekseevich Solodkij
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Full Range ◽  
Mrna Level ◽  
Xenograft Model ◽  
Specific Inhibitor ◽  
Antitumor Effects ◽  
Mcf 7

e13545 Background: MM-D37K is a synthetic peptide which consists of p16INK4a-specific inhibitor of complex cyclin D- CDK4 and CDK6 and cell penetrating peptide (CPP) – Antp (Penetratin). We investigated in vitro and in vivo cytotoxic, cytostatic and antitumor activity of MM-D37K. The level of cyclin A, Ki67,bax, bcl-2 and pRb phosphorylation was investigated. Full range of Toxicology tests and Pharmacokinetics experiments in mice, rats and rabbits were performed. Methods: Different cell lines (Jurcat, Raji, A549, MCF-7, Hct-116, Ht-29, HEK293) were incubated with 0.1-100 mM MM-D37K for 24-48 hrs. Proliferation (MTT), DNA-content, cell cycle (flow cytometry) and mRNA level of appropriate proteins (RT PCR) were investigated. In vivo experiments were conducted on xenograft model of HCT116, A-549 at concentration 5 and 10 mg/kg of MM-D37K. Toxicology experiments were made under RF Law and included 3 types of animals. LC-MS MMD37K method of detection in plasma was developed. Results: MM-D37K prevented pRb phosphorilation and proliferation activation in all investigated cell lines. Cell cycle was blocked in G1 phase. Cytostatic effect did not depend on p16 mutation or expression. MM-D37K induced apoptosis in 20-82% of investigated cells at 40 mM with lowest level for MCF-7. LD10 for rats was 100 mg/kg and no deaths were registered for rabbits (highest dose was 50 mg/kg). Concentration of MMD-37K in plasma after 2 min and bolus i.v. injection in dose 10 mg/kg was 72.16±5.64 mcg/ml. Concentration decreased in two phases. 1st – t1/2 = 2.39±0.39 min and for 2nd t1/2=2.39±0.39 hr. Antitumor effects in xenograft model were 53% for A-549 and 67% for HCT116. Conclusions: Our results proved cytotoxic, cytostatic and antitumor effects of MM-D37K in investigated cell lines in vitro and in vivo. Toxicological and pharmacokinetics results allow us recommend for I/IIa Phase clinical trial. (Support: MetaMax Ltd., RFFI, Minpromtorg RF.)

scholarly journals Synthesis and high antiproliferative activity of dehydroabietylamine pyridine derivatives in vitro and in vivo

2020 ◽  
Vol 477 (12) ◽  
pp. 2383-2399
Author(s):  
Fengyi Zhao ◽  
Wen Lu ◽  
Yuanyuan Xu ◽  
Li Xu ◽  
Jingjing Zhang ◽  
...  
Keyword(s):  
Umbilical Vein ◽  
A549 Cells ◽  
Great Promise ◽  
Pyridine Derivatives ◽  
Inhibition Rate ◽  
Low Toxicity ◽  
A549 Lung ◽  
Mcf 7

Several bioactive dehydroabietylamine Schiff-bases (L1−L4), amides (L5−L11) and complex CuL3(NO3)2, Cu(L5)3, Co(L6)2Cl2 had been synthesized successfully for developing more efficient but lower toxic antiproliferative compounds. Their antiproliferative activities to Hela (cervix), HepG2 (liver), MCF-7 (breast), A549 (lung) and HUVEC (umbilical vein, normal cell) were investigated in vitro. The toxicity of all compounds was less than dehydroabietylamine (L0). For HepG2 cells, L1, L2 and L3 had higher anti-HepG2 activity, especially L1 (0.52 µM) had highest anti-HepG2 activity but low toxicity. For MCF-7 cells, L1, L2, L3 and L4 had higher anti-MCF-7 activity, especially L3(0.49 µM) had highest anti-MCF-7 activity but low toxicity. For A549 cells, L2 and L3 had higher anti-A549 activity. Furthermore, L1 and L3 may be the great promise antiproliferative drugs with nontoxic side effects, due to the high anti-HepG2 and anti-MCF-7 inhibition rate in vivo, 65% and 61%, respectively. L1, L2 and L3 could induce apoptosis through intercalating into DNA.

Applications of ROS-Induced Zr-MOFs Platform in Multimodal Synergistic Therapy

2021 ◽  
Vol 21 ◽  
Author(s):  
Qiongjie Ding ◽  
Yiwei Liu ◽  
Chuncheng Shi ◽  
Jifei Xiao ◽  
Wei Dai ◽  
...  
Keyword(s):  
Drug Delivery ◽  
High Efficiency ◽  
Tumor Therapy ◽  
Antitumor Effects ◽  
Metal Organic ◽  
Low Toxicity ◽  
Therapeutic Mechanisms ◽  
Biological Performance

Background: Metal-organic frameworks (MOFs) exhibited the adjustable aperture, high load capacities, tailorable structures, and excellent biocompatibilities that have used to be as drug delivery carries in cancer therapy. Until now, Zr-MOFs in particular combine optimal stability towards hydrolysis and postsynthetic modification with low toxicity, and are widely studied for its excellent biological performance. Introduction: This review comprises the exploration of Zr-MOFs as drug delivery devices (DDSs) with focus on various new methods, including chemotherapy (CT), photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy(SDT), radiotherapy, immunotherapy, gene therapy and related combined therapies, which all generate reactive oxygen species (ROS) to achieve the high efficiency of tumor therapy. Conclusion: We described and summarized these pertinent examples of the therapeutic mechanisms and highlight the antitumor effects of their biological application both in vitro and in vivo. The perspectives on their future applications and analogous challenge of the Zr-MOFs materials are given.

In vitro trans-scleral iontophoresis of methylprednisolone hemisuccinate with short application time and high drug concentration

2013 ◽  
Vol 451 (1-2) ◽  
pp. 12-17 ◽  
Author(s):  
S. Pescina ◽  
D. Martini ◽  
P. Santi ◽  
C. Padula ◽  
L. Murtomäki ◽  
...  
Keyword(s):  
Drug Concentration ◽  
Application Time ◽  
High Drug ◽  
High Drug Concentration

Development of a multifunctional gold nanoplatform for combined chemo-photothermal therapy against oral cancer

Nanomedicine ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. 661-676 ◽  
Author(s):  
Zengying Liu ◽  
Jianbo Shi ◽  
Bangshang Zhu ◽  
Qin Xu
Keyword(s):  
Drug Delivery ◽  
Oral Cancer ◽  
Photothermal Therapy ◽  
Drug Loading ◽  
Antitumor Efficacy ◽  
Antitumor Effects ◽  
In Vivo Experiments ◽  
Low Toxicity

Aim: To design and fabricate a multifunctional drug-delivery nanoplatform for oral cancer therapy. Materials & methods: Polyethylene glycol-stabilized, PDPN antibody (PDPN Ab)- and doxorubicin (DOX)-conjugated gold nanoparticles (AuNPs) were prepared and evaluated for their cytotoxicity and antitumor efficacy in both chemotherapy and photothermal therapy. Results: The obtained (PDPN Ab)-AuNP-DOX system presents low toxicity, a high drug loading capacity and cellular uptake efficiency. Both in vitro and in vivo experiments demonstrate that (PDPN Ab)-AuNP-DOX has enhanced antitumor efficacy. Treatment with (PDPN Ab)-AuNP-DOX combined with laser irradiation exhibits superior antitumor effects. Conclusion: This (PDPN Ab)-AuNP-DOX system may be used as a versatile drug-delivery nanoplatform for targeted and combined chemo-photothermal therapy against oral cancer.

scholarly journals Anticancer Activities of Thymus vulgaris L. in Experimental Breast Carcinoma in Vivo and in Vitro

2019 ◽  
Vol 20 (7) ◽  
pp. 1749 ◽  
Author(s):  
Kubatka ◽  
Uramova ◽  
Kello ◽  
Kajo ◽  
Samec ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Methylation Status ◽  
Thymus Vulgaris ◽  
Control Analysis ◽  
Gene Promoters ◽  
Antitumor Effects ◽  
Mammary Carcinomas ◽  
Mcf 7

Naturally-occurring mixtures of phytochemicals present in plant foods are proposed to possess tumor-suppressive activities. In this work, we aimed to evaluate the antitumor effects of Thymus vulgaris L. in in vivo and in vitro mammary carcinoma models. Dried T. vulgaris (as haulm) was continuously administered at two concentrations of 0.1% and 1% in the diet in a chemically-induced rat mammary carcinomas model and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular analyses of rodent mammary carcinomas were performed. In addition, in vitro evaluations using MCF-7 and MDA-MB-231 cells were carried out. In mice, T. vulgaris at both doses reduced the volume of 4T1 tumors by 85% (0.1%) and 84% (1%) compared to the control, respectively. Moreover, treated tumors showed a substantial decrease in necrosis/tumor area ratio and mitotic activity index. In the rat model, T. vulgaris (1%) decreased the tumor frequency by 53% compared to the control. Analysis of the mechanisms of anticancer action included well-described and validated diagnostic and prognostic markers that are used in both clinical approach and preclinical research. In this regard, the analyses of treated rat carcinoma cells showed a CD44 and ALDH1A1 expression decrease and Bax expression increase. Malondialdehyde (MDA) levels and VEGFR-2 expression were decreased in rat carcinomas in both the T. vulgaris treated groups. Regarding the evaluations of epigenetic changes in rat tumors, we found a decrease in the lysine methylation status of H3K4me3 in both treated groups (H3K9m3, H4K20m3, and H4K16ac were not changed); up-regulations of miR22, miR34a, and miR210 expressions (only at higher doses); and significant reductions in the methylation status of four gene promoters—ATM serin/threonine kinase, also known as the NPAT gene (ATM); Ras-association domain family 1, isoform A (RASSF1); phosphatase and tensin homolog (PTEN); and tissue inhibitor of metalloproteinase-3 (TIMP3) (the paired-like homeodomain transcription factor (PITX2) promoter was not changed). In vitro study revealed the antiproliferative and proapoptotic effects of essential oils of T. vulgaris in MCF-7 and MDA-MB-231 cells (analyses of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS); 5-bromo-20-deoxyuridine (BrdU); cell cycle; annexin V/PI; caspase-3/7; Bcl-2; PARP; and mitochondrial membrane potential). T. vulgaris L. demonstrated significant chemopreventive and therapeutic activities against experimental breast carcinoma.

Sign in / Sign up

Export Citation Format

Share Document