scholarly journals Preclinical therapeutics ex ovo quail eggs as a biomimetic automation-ready xenograft platform

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samuel V. Rasmussen ◽  
Noah E. Berlow ◽  
Lisa Hudson Price ◽  
Atiya Mansoor ◽  
Stefano Cairo ◽  
...  
Keyword(s):  
Drug Toxicity ◽  
Screening Method ◽  
Chorioallantoic Membrane ◽  
Drug Efficacy ◽  
Cost Effective ◽  
Coturnix Japonica ◽  
In Vivo Studies ◽  
Anti Cancer

AbstractPreclinical cancer research ranges from in vitro studies that are inexpensive and not necessarily reflective of the tumor microenvironment to mouse studies that are better models but prohibitively expensive at scale. Chorioallantoic membrane (CAM) assays utilizing Japanese quail (Coturnix japonica) are a cost-effective screening method to precede and minimize the scope of murine studies for anti-cancer efficacy and drug toxicity. To increase the throughput of CAM assays we have built and optimized an 11-day platform for processing up to 200 quail eggs per screening to evaluate drug efficacy and drug toxicity caused by a therapeutic. We demonstrate ex ovo concordance with murine in vivo studies, even when the in vitro and in vivo studies diverge, suggesting a role for this quail shell-free CAM xenograft assay in the validation of new anti-cancer agents.

scholarly journals The Occurrence and Biological Activity of Tormentic Acid—A Review

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3797
Author(s):  
Marta Olech ◽  
Wojciech Ziemichód ◽  
Natalia Nowacka-Jechalke
Keyword(s):  
Biological Activity ◽  
Plant Species ◽  
Current Knowledge ◽  
In Vivo Studies ◽  
Natural Sources ◽  
Anti Cancer ◽  
Biochemical Mechanisms ◽  
Tormentic Acid

This review focuses on the natural sources and pharmacological activity of tormentic acid (TA; 2α,3β,19α-trihydroxyurs-2-en-28-oic acid). The current knowledge of its occurrence in various plant species and families is summarized. Biological activity (e.g., anti-inflammatory, antidiabetic, antihyperlipidemic, hepatoprotective, cardioprotective, neuroprotective, anti-cancer, anti-osteoarthritic, antinociceptive, antioxidative, anti-melanogenic, cytotoxic, antimicrobial, and antiparasitic) confirmed in in vitro and in vivo studies is compiled and described. Biochemical mechanisms affected by TA are indicated. Moreover, issues related to the biotechnological methods of production, effective eluents, and TA derivatives are presented.

scholarly journals Design and Characterization of Combinational Domperidone-Famotidine Floating Drug Delivery System - In vitro and In vivo studies

2021 ◽  
Vol 62 (2) ◽  
pp. 144-162
Author(s):  
Mounika Chidurala ◽  
Raveendra Reddy J
Keyword(s):  
Drug Release ◽  
Oral Administration ◽  
Quality By Design ◽  
Release Kinetics ◽  
Cost Effective ◽  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Studies

Introduction: The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and releasethe drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach. Method: Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes)wereidentified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23factor experimental design with midpoints was selected for statistical analysis and optimization. Results: HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit’s stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2 of an optimized product when compared to the marketed product. Conclusions: It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula.

Viscum album (L) extracts in cancer treatment: a systematic review of in vitro and in vivo studies

2021 ◽  
Vol 14 (2) ◽  
pp. 52-52
Author(s):  
Aloisio Cunha de Carvalho ◽  
Leoni Villano Bonamin
Keyword(s):  
Systematic Review ◽  
Experimental Studies ◽  
Pharmaceutical Preparations ◽  
Viscum Album ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Pubmed Database ◽  
Anti Cancer

Background: Several reviews about phytotherapy and homeopathy have been published in the last years, including Viscum album (VA.L). VA is a parasite plant whose extract has anti-cancer proprieties and is used alone or in combination with conventional chemotherapy. Methods: We performed a systematic review about the in vivo and in vitro models described in the literature, including veterinary clinical trials. The literature was consulted from Pubmed database. Results: There are several kinds of pharmaceutical preparations about VA and their active principles used in experimental studies, lectin being frequently studied (alone or as an extract compound). More than 50% of available literature about VA is related to the lectin effects. On the other hand, the effects of viscotoxins are less studied. Among the in vivo experimental studies about VA and its compounds, the B16 murine melanoma is the most used model, followed by Ehrlich, Walker and Dalton tumors. The results point to the apoptotic effects, metastasis control and tumor regression. Some veterinary clinical studies about the use of VA in the treatment of sarcoid, fibrosarcoma and neuroblastoma are quoted in literature too, with interesting results. Considering the in vitro models, our review revealed that NALM6 leukemia cells, B16 melanoma and NC1-H460 lung carcinoma were the most studied tumor models, apoptosis signals being the most important findings. Only one study verified immunoglobulin and interleukin production. All consulted papers were related to phytotherapy preparations only. Conclusions: Although the literature about the anti-cancer activity of VA extract and its lectins is enough, there is a marked lack of information about viscotoxin activities and about the effects of homeopathic preparations of this plant on animal tumors and on in vitro cultivated tumor cells.

Quality by Design enabled anti-hypertensive Floating drug delivery system by Risk assessment and Design of Experiment (DoE) – In vitro – In vivo correlation studies

2021 ◽  
Vol 16 ◽  
Author(s):  
Mounika Chidurala ◽  
Raveendra Reddy J
Keyword(s):  
Drug Release ◽  
Risk Analysis ◽  
Quality By Design ◽  
Release Kinetics ◽  
Cost Effective ◽  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Studies

Background: The present research aimed to develop and optimize extended-release floating tablets of Sacubitril and Valsartan through Quality by Design (QbD) approach. Risk analysis by formulation assessment and process parameters showed that optimizing the levels of the polymer will minimize high risk to meet the target profile. A two (2) level three (3) full factorial experimental design along with midpoints was carefully chosen for optimization and statistical analysis. Based on the literature, the independent and dependent variables were selected. Results: HPMC K100, Carbopol 934P had a positive effect, whereas Ethylcellulose had a negative effect on Floating time, drug release at 2 h, drug release at 12 h and, 50% responses. Drug release kinetics followed the first-order release with Higuchi and Fickian diffusion. Contour and overlay plots were utilized for an assortment of design space and optimized formula. ANOVA results of all the factors exhibited significance at p<0.05. Abdominal X-ray imaging of the optimized tablets on healthy rabbit’s stomach confirmed the floating behavior for more than 12 h. In vivo pharmacokinetic studies in rabbits showed that the optimized formulation exhibited prolonged and extended drug release with improved Cmax, tmax, AUCo-t, and t1/2 of test product when compared to marketed product. IVIVC model was developed by using dissolution data of in vitro and pharmacokinetics data of in-vivo by de-convolution method (Wagner-Nelson method). Conclusion: The Quality by Design implementation in the formulation and optimization abridged the number of trials to produce a cost-effective formula. In vivo studies confirmed that the formula was successfully developed with extended floating time (12 h) and drug release by risk analysis and experimental designs. Level A correlation was observed which confirmed a good correlation between in vitro and in vivo data.

scholarly journals Impact of Mucin on Drug Diffusion: Development of a Straightforward In Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 168 ◽  
Author(s):  
Margherita Falavigna ◽  
Paul Stein ◽  
Gøril Flaten ◽  
Massimiliano di Cagno
Keyword(s):  
Drug Interaction ◽  
Drug Absorption ◽  
Cost Effective ◽  
Physicochemical Characteristics ◽  
In Vivo Studies ◽  
Phospholipid Vesicle ◽  
Mucus Layer ◽  
The Impact

Mucosal drug delivery accounts for various administration routes (i.e., oral, vaginal, ocular, pulmonary, etc.) and offers a vast surface for the permeation of drugs. However, the mucus layer which shields and lubricates all mucosal tissues can compromise drugs from reaching the epithelial site, thus affecting their absorption and therapeutic effect. Therefore, the effect of the mucus layer on drug absorption has to be evaluated early in the drug-development phase, prior to in vivo studies. For this reason, we developed a simple, cost-effective and reproducible method employing UV-visible localized spectroscopy for the assessment of the interaction between mucin and drugs with different physicochemical characteristics. The mucin–drug interaction was investigated by measuring the drug relative diffusivity (Drel) in the presence of mucin, and the method was validated by fitting experimental and mathematical data. In vitro permeability studies were also performed using the mucus-covered artificial permeation barrier (mucus–PVPA, Phospholipid Vesicle-based Permeation Assay) for comparison. The obtained results showed that the diffusion of drugs was hampered by the presence of mucin, especially at higher concentrations. This novel method proved to be suitable for the investigation on the extent of mucin–drug interaction and can be successfully used to assess the impact that the mucus layer has on drug absorption.

scholarly journals Angiostatic activity of the antitumor cytokine interleukin-21

Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 4940-4947 ◽  
Author(s):  
Karolien Castermans ◽  
Sebastien P. Tabruyn ◽  
Rong Zeng ◽  
Judy R. van Beijnum ◽  
Cheryl Eppolito ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Angiogenesis ◽  
Chorioallantoic Membrane ◽  
Antitumor Immune Response ◽  
In Vivo Studies ◽  
Type I ◽  
Stat3 Phosphorylation ◽  
Interleukin 21

Abstract Interleukin-21 (IL-21) is a recently described immunoregulatory cytokine. It has been identified as a very potent immunotherapeutic agent in several cancer types in animal models, and clinical studies are ongoing. IL-21 belongs to the type I cytokine family of which other members, ie, IL-2, IL-15, and IL-4, have been shown to exert activities on vascular endothelial cells (ECs). We hypothesized that IL-21, in addition to inducing the antitumor immune response, also inhibits tumor angiogenesis. In vitro experiments showed a decrease of proliferation and sprouting of activated ECs after IL-21 treatment. We found that the IL-21 receptor is expressed on vascular ECs. Furthermore, in vivo studies in the chorioallantoic membrane of the chick embryo and in mouse tumors demonstrated that IL-21 treatment disturbs vessel architecture and negatively affects vessel outgrowth. Our results also confirm the earlier suggested angiostatic potential of IL-2 in vitro and in vivo. The angiostatic effect of IL-21 is confirmed by the decrease in expression of angiogenesis-related genes. Interestingly, IL-21 treatment of ECs leads to a decrease of Stat3 phosphorylation. Our research shows that IL-21 is a very powerful antitumor compound that combines the induction of an effective antitumor immune response with inhibition of tumor angiogenesis.

scholarly journals New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1523 ◽  
Author(s):  
Yuanyuan Fu ◽  
Qianqian Gu ◽  
Li Luo ◽  
Jiecheng Xu ◽  
Yuping Luo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Therapy ◽  
Therapeutic Strategy ◽  
Screening Method ◽  
Cancer Drug ◽  
Autophagic Flux ◽  
Single Target ◽  
Anti Cancer

Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy. Although some inhibitors of either lysosome or ATG4B were reported, there are limitations in the use of these single target compounds. Considering multi-functional drugs have advantages, such as high efficacy and low toxicity, we first screened and validated a batch of compounds designed and synthesized in our laboratory by combining the screening method of ATG4B inhibitors and the identification method of lysosome inhibitors. ATG4B activity was effectively inhibited in vitro. Moreover, 163N inhibited autophagic flux and caused the accumulation of autolysosomes. Further studies demonstrated that 163N could not affect the autophagosome-lysosome fusion but could cause lysosome dysfunction. In addition, 163N diminished tumor cell viability and impaired the development of colorectal cancer in vivo. The current study findings indicate that the dual effect inhibitor 163N offers an attractive new anti-cancer drug and compounds having a combination of lysosome inhibition and ATG4B inhibition are a promising therapeutic strategy for colorectal cancer therapy.

scholarly journals ANTICANCER ACTIVITY OF UPAVISHA ARKA: AN OVERVIEW

2020 ◽  
Vol 9 (6) ◽  
pp. 175-181
Author(s):  
Chandekar Deepali Boudhadas ◽  
Pawade Uday Venkatrao ◽  
Nikam Ashwin Vithalrao ◽  
Anjankar Meghsham Pramodrao
Keyword(s):  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Anticancer Drug ◽  
Cost Effective ◽  
In Vivo Studies ◽  
Calotropis Procera ◽  
Calotropis Gigantea ◽  
Natural Derivative

Cancer is one amongst the dreadful diseases of present century. The incidence of cancer is increasing worldwide. Every year about 8,00,000 new cancer patients get registered with the national cancer registry program in India. Ayurveda an ancient Indian medicine science describes many useful herbal drugs for such types of advanced diseases. Upavisha the plant poisons of low potency are mentioned in Agadtantra. Arka (Calotropis procera/ Calotropis gigantea) is one among these Upavisha is emerging as an effective anticancer drug. It shows various pharmacological activities such as Anticancer, Antimicrobial, Antiimplantation etc. Different parts of Arka are used to treat cancer. In current scenario number of synthetic anticancer drugs are used to treat cancer. These synthetic anticancer drugs are expensive and shows harmful adverse effects. Upavisha like Arka which is natural derivative may be cost effective & less harmful as Anticancer drug. Anticancer activity of Calotropis procera/Calotropis gigantea is reported in scientific journals. This review summarizes various In Vitro and In Vivo studies of anticancer activity of Upavisha Arka.

scholarly journals PHYTOPHARMACOLOGY OF HOLMSKIOLDIA SANGUINEA RETZ.: A REVIEW

2021 ◽  
Vol 12 (6) ◽  
pp. 52-59
Author(s):  
Rajeev Sati ◽  
Monika Bisht
Keyword(s):  
Asia Pacific ◽  
In Vivo Studies ◽  
Anticancer Properties ◽  
Anti Cancer ◽  
Central Nervous System Depressant ◽  
Botanical Description ◽  
Plant Constituents ◽  
Phytochemical Constituents

Holmskioldia sanguinea Retz. is a Sub-Himalayan plant that has been cultivated in the Americas, Europe, Indo-china, Asia-Pacific, and Southern Africa. It has been used traditionally to treat rheumatism and rheumatoid arthritis, dysentery, headaches, hypertension, boils, blain, ulcers, and gynaecological problems, as well as a blood purifying concoction. The botanical description of the plant, its phytochemical constituents, and its pharmacological activities are discussed, with an emphasis on antibacterial, antihepatotoxic, antifungal, anti-inflammatory, antioxidant, antimicrobial, analgesic, central nervous system depressant, diuretic, oestrogenic, anti-implantation, and anticancer properties. Most pharmacological effects are a result of plant constituents such as alkaloids, terpenoids, tannins, flavonoids, glycosides and phenols, to name a few. Conventional wisdom should be confirmed through in vitro and in vivo studies, as well as clinical trials. Herb's anti-tumor and anti-cancer properties have generated significant interest.

The Anticancer Effect of Sanguinarine: A Review

2018 ◽  
Vol 24 (24) ◽  
pp. 2760-2764 ◽  
Author(s):  
Chenxing Fu ◽  
Guiping Guan ◽  
Hongbing Wang
Keyword(s):  
Tumor Cell ◽  
In Vivo Studies ◽  
Inhibitory Effects ◽  
Anticancer Effect ◽  
Growth Inhibitory ◽  
Cell Proliferation Inhibition ◽  
Anti Cancer ◽  
Induced Apoptosis

In vitro and in vivo studies have revealed that Sanguinarine has antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects on tumor cells of a variety of cancers. Previous research showed that sanguinarine induced apoptosis (cell death) and/or antiproliferative while reducing tumor cell antiangiogenic and anti-invasive properties. This paper describes various sanguinarine anti-cancer mechanisms, including inhibition of erroneously-activated signal transduction pathways, apoptosis, and tumor cell proliferation inhibition.

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