scholarly journals Evaluation of Novel Doxorubicin-Loaded Magnetic Wax Nanocomposite Vehicles as Cancer Combinatorial Therapy Agents

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 637
Author(s):  
Julia Jiménez-López ◽  
Lorena García-Hevia ◽  
Consolación Melguizo ◽  
Jose Prados ◽  
Manuel Bañobre-López ◽  
...  
Keyword(s):  
Preliminary Data ◽  
3D Models ◽  
In Vitro Models ◽  
Solid Tumours ◽  
Clinical Translation ◽  
Combinatorial Therapy ◽  
New Developments ◽  
In Vivo Tests

The development of nanotechnology-based solutions for cancer at a preclinical level advances at an astounding pace. So far, clinical translation of these new developments has not been able to keep the pace due to a range of different reasons. One of them is the mismatch between in vitro and in vivo results coming from the expected difference in complexity. To overcome this problem, extensive characterisation using advanced in vitro models can lead to stronger preliminary data to face in vivo tests. Here, a comprehensive in vitro validation of a combinatorial therapy nanoformulation against solid tumours is presented. The information extracted from the different in vitro models highlights the importance of advanced 3D models to fully understand the potential of this type of complex drugs.

In Vitro Methods as a Tool in Neurotoxicity Studies

1995 ◽  
Vol 23 (4) ◽  
pp. 491-496
Author(s):  
Hanna Tähti ◽  
Leila Vaalavirta ◽  
Tarja Toimela
Keyword(s):  
Risk Evaluation ◽  
Toxicity Testing ◽  
In Vitro Models ◽  
In Vitro Tests ◽  
Industrial Chemicals ◽  
Mercury Compounds ◽  
Toxicological Data ◽  
In Vivo Tests

— There are several hundred industrial chemicals with neurotoxic potential. The neurotoxic risks of most of these chemicals are unknown. Additional methods are needed to assess the risks more effectively and to elucidate the mechanisms of neurotoxicity more accurately than is possible with the conventional methods. This paper deals with general tasks concerning the use of in vitro models in the evaluation of neurotoxic risks. It is based on our previous studies with various in vitro models and on recent literature. The induction of glial fibrillary acidic protein in astrocyte cultures after treatment with known neurotoxicants (mercury compounds and aluminium) is discussed in more detail as an important response which can be detected in vitro. When used appropriately with in vivo tests and with previous toxicological data, in vitro neurotoxicity testing considerably improves risk assessment. The incorporation of in vitro tests into the early stages of risk evaluation can reduce the number of animals used in routine toxicity testing, by identifying chemicals with high neurotoxic potential.

scholarly journals The Role of Biomimetic Hypoxia on Cancer Cell Behaviour in 3D Models: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1334
Author(s):  
Ye Liu ◽  
Zahra Mohri ◽  
Wissal Alsheikh ◽  
Umber Cheema
Keyword(s):  
Systematic Review ◽  
Cellular Response ◽  
3D Culture ◽  
3D Models ◽  
In Vitro Models ◽  
Research Findings ◽  
Tissue Models

The development of biomimetic, human tissue models is recognized as being an important step for transitioning in vitro research findings to the native in vivo response. Oftentimes, 2D models lack the necessary complexity to truly recapitulate cellular responses. The introduction of physiological features into 3D models informs us of how each component feature alters specific cellular response. We conducted a systematic review of research papers where the focus was the introduction of key biomimetic features into in vitro models of cancer, including 3D culture and hypoxia. We analysed outcomes from these and compiled our findings into distinct groupings to ascertain which biomimetic parameters correlated with specific responses. We found a number of biomimetic features which primed cancer cells to respond in a manner which matched in vivo response.

Mycotoxin mechanisms of action and health impact: ‘in vitro’ or ‘in vivo’ tests, that is the question

2015 ◽  
Vol 8 (5) ◽  
pp. 573-589 ◽  
Author(s):  
F. Cheli ◽  
C. Giromini ◽  
A. Baldi
Keyword(s):  
Health Effects ◽  
Health Impact ◽  
In Vitro Models ◽  
Mechanisms Of Action ◽  
Animal Testing ◽  
Suitable Alternative ◽  
In Vivo Tests ◽  
Contaminated Food

The aim of this paper is to present examples of in vitro and in vivo tests for mycotoxin mechanisms of action and evaluation of health effects, with a focus on the gut environment and toxicity testing. In vivo investigations may provide information on the net effects of mycotoxins in whole animals, whereas in vitro models represent effective tools to perform simplified experiments under uniform and well-controlled conditions and a suitable alternative to in vivo animal testing providing insights not achievable with animal studies. The main limits of in vitro models are the lack of interactions with other cells and extracellular factors, lack of hormonal or immunological influences, and lack or different levels of in vitro expression of genes involved in the overall response to mycotoxins. The translation of in vitro data into meaningful in vivo effects remains an unsolved problem. The main issues to be considered are the mycotoxin concentration range in accordance with levels encountered in realistic situations, the identification of reliable biomarkers of mycotoxin toxicity, the measurement of the chronic toxicity, the evaluation of single- or multi-toxin challenge. The gastrointestinal wall is the first barrier preventing the entry of undesirable substances. The intestinal epithelium can be exposed to high concentrations of mycotoxins upon ingestion of contaminated food and the amount of mycotoxin consumed via food does not always reflect the amount available to exert toxic actions in a target organ. In vitro digestion models in combination with intestinal epithelial cells are powerful tools to screen and predict the in vivo bioavailability and digestibility of mycotoxins in contaminated food and correctly estimate health effects. In conclusion, in vitro and in vivo tests are complementary approaches for providing a more accurate picture of the health impact of mycotoxins and improved understanding and evaluation of relevant dietary exposure and risk scenarios.

scholarly journals Fracture Healing Research—Shift towards In Vitro Modeling?

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 748
Author(s):  
Moritz Pfeiffenberger ◽  
Alexandra Damerau ◽  
Annemarie Lang ◽  
Frank Buttgereit ◽  
Paula Hoff ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Ex Vivo ◽  
3D Models ◽  
In Vitro Models ◽  
Human Patient ◽  
In Vivo Models ◽  
Underlying Mechanisms ◽  
Biological Situation

Fractures are one of the most frequently occurring traumatic events worldwide. Approximately 10% of fractures lead to bone healing disorders, resulting in strain for affected patients and enormous costs for society. In order to shed light into underlying mechanisms of bone regeneration (habitual or disturbed), and to develop new therapeutic strategies, various in vivo, ex vivo and in vitro models can be applied. Undeniably, in vivo models include the systemic and biological situation. However, transferability towards the human patient along with ethical concerns regarding in vivo models have to be considered. Fostered by enormous technical improvements, such as bioreactors, on-a-chip-technologies and bone tissue engineering, sophisticated in vitro models are of rising interest. These models offer the possibility to use human cells from individual donors, complex cell systems and 3D models, therefore bridging the transferability gap, providing a platform for the introduction of personalized precision medicine and finally sparing animals. Facing diverse processes during fracture healing and thus various scientific opportunities, the reliability of results oftentimes depends on the choice of an appropriate model. Hence, we here focus on categorizing available models with respect to the requirements of the scientific approach.

scholarly journals Advances in Non-Animal Testing Approaches towards Accelerated Clinical Translation of Novel Nanotheranostic Therapeutics for Central Nervous System Disorders

Nanomaterials ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2632
Author(s):  
Mark J. Lynch ◽  
Oliviero L. Gobbo
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Rational Design ◽  
In Vitro Models ◽  
Clinical Translation ◽  
Clinical Testing ◽  
Cns Disorders ◽  
Novel Drug

Nanotheranostics constitute a novel drug delivery system approach to improving systemic, brain-targeted delivery of diagnostic imaging agents and pharmacological moieties in one rational carrier platform. While there have been notable successes in this field, currently, the clinical translation of such delivery systems for the treatment of neurological disorders has been limited by the inadequacy of correlating in vitro and in vivo data on blood–brain barrier (BBB) permeation and biocompatibility of nanomaterials. This review aims to identify the most contemporary non-invasive approaches for BBB crossing using nanotheranostics as a novel drug delivery strategy and current non-animal-based models for assessing the safety and efficiency of such formulations. This review will also address current and future directions of select in vitro models for reducing the cumbersome and laborious mandate for testing exclusively in animals. It is hoped these non-animal-based modelling approaches will facilitate researchers in optimising promising multifunctional nanocarriers with a view to accelerating clinical testing and authorisation applications. By rational design and appropriate selection of characterised and validated models, ranging from monolayer cell cultures to organ-on-chip microfluidics, promising nanotheranostic particles with modular and rational design can be screened in high-throughput models with robust predictive power. Thus, this article serves to highlight abbreviated research and development possibilities with clinical translational relevance for developing novel nanomaterial-based neuropharmaceuticals for therapy in CNS disorders. By generating predictive data for prospective nanomedicines using validated in vitro models for supporting clinical applications in lieu of requiring extensive use of in vivo animal models that have notable limitations, it is hoped that there will be a burgeoning in the nanotherapy of CNS disorders by virtue of accelerated lead identification through screening, optimisation through rational design for brain-targeted delivery across the BBB and clinical testing and approval using fewer animals. Additionally, by using models with tissue of human origin, reproducible therapeutically relevant nanomedicine delivery and individualised therapy can be realised.

scholarly journals Application of three-dimensional neuronal cell cultures in the studies of mechanisms of neurodegenerative diseases

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Anna Słońska ◽  
Joanna Cymerys
Keyword(s):  
Neurodegenerative Diseases ◽  
Cell Cultures ◽  
Three Dimensional ◽  
Neuronal Cell ◽  
3D Models ◽  
In Vitro Models ◽  
Gene And Protein Expression ◽  
Or Gene

In vitro models utilizing cells in planar two-dimensional (2D) cultures do not reflect the in vivo environment and are increasingly replaced by three-dimensional (3D) cultures. Fundamental differences between 2D and 3D cell cultures systems include cell attach, spread and grow, their morphology, proliferation, differentiation or gene and protein expression. For that reason 3D models have been proven to be invaluable tools of study for the various fields of science, such as drug discovery, cancer research, differentiation studies or neuroscience. In the present review, we discuss 3D neural in vitro models that might provide important insides about the mechanisms of pathogenesis of neurodegenerative diseases.

scholarly journals Genotoxicity of Nanomaterials: Advanced In Vitro Models and High Throughput Methods for Human Hazard Assessment—A Review

Nanomaterials ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1911 ◽  
Author(s):  
Yvonne Kohl ◽  
Elise Rundén-Pran ◽  
Espen Mariussen ◽  
Michelle Hesler ◽  
Naouale El Yamani ◽  
...  
Keyword(s):  
High Throughput ◽  
State Of The Art ◽  
Genetic Material ◽  
3D Models ◽  
In Vitro Models ◽  
Current State ◽  
Genotoxic Compounds ◽  
Genome Level

Changes in the genetic material can lead to serious human health defects, as mutations in somatic cells may cause cancer and can contribute to other chronic diseases. Genotoxic events can appear at both the DNA, chromosomal or (during mitosis) whole genome level. The study of mechanisms leading to genotoxicity is crucially important, as well as the detection of potentially genotoxic compounds. We consider the current state of the art and describe here the main endpoints applied in standard human in vitro models as well as new advanced 3D models that are closer to the in vivo situation. We performed a literature review of in vitro studies published from 2000–2020 (August) dedicated to the genotoxicity of nanomaterials (NMs) in new models. Methods suitable for detection of genotoxicity of NMs will be presented with a focus on advances in miniaturization, organ-on-a-chip and high throughput methods.

scholarly journals In Vitro and In Vivo Models to Assess the Immune-Related Effects of Nanomaterials

2021 ◽  
Vol 18 (22) ◽  
pp. 11769
Author(s):  
Diana Boraschi ◽  
Dongjie Li ◽  
Yang Li ◽  
Paola Italiani
Keyword(s):  
Real Life ◽  
Relevant Information ◽  
3D Models ◽  
In Vitro Models ◽  
Experimental Models ◽  
Human Beings ◽  
In Vivo Models ◽  
Advantages And Disadvantages

The immunological safety of drugs, nanomaterials and contaminants is a central point in the regulatory evaluation and safety monitoring of working and public places and of the environment. In fact, anomalies in immune responses may cause diseases and hamper the physical and functional integrity of living organisms, from plants to human beings. In the case of nanomaterials, many experimental models are used for assessing their immunosafety, some of which have been adopted by regulatory bodies. All of them, however, suffer from shortcomings and approximations, and may be inaccurate in representing real-life responses, thereby leading to incomplete, incorrect or even misleading predictions. Here, we review the advantages and disadvantages of current nanoimmunosafety models, comparing in vivo vs. in vitro models and examining the use of animal vs. human cells, primary vs. transformed cells, complex multicellular and 3D models, organoids and organs-on-chip, in view of implementing a reliable and personalized nanoimmunosafety testing. The general conclusion is that the choice of testing models is key for obtaining reliable predictive information, and therefore special attention should be devoted to selecting the most relevant and realistic suite of models in order to generate relevant information that can allow for safer-by-design nanotechnological developments.

scholarly journals Looking for In Vitro Models for Retinal Diseases

2021 ◽  
Vol 22 (19) ◽  
pp. 10334
Author(s):  
Margherita Alfonsetti ◽  
Vanessa Castelli ◽  
Michele d’Angelo ◽  
Elisabetta Benedetti ◽  
Marcello Allegretti ◽  
...  
Keyword(s):  
Visual Function ◽  
Retinal Disease ◽  
3D Models ◽  
In Vitro Models ◽  
Retinal Diseases ◽  
In Vivo Models ◽  
In Vivo Experiments ◽  
Toxicological Studies

Retina is a layered structure of the eye, composed of different cellular components working together to produce a complex visual output. Because of its important role in visual function, retinal pathologies commonly represent the main causes of visual injury and blindness in the industrialized world. It is important to develop in vitro models of retinal diseases to use them in first screenings before translating in in vivo experiments and clinics. For this reason, it is important to develop bidimensional (2D) models that are more suitable for drug screening and toxicological studies and tridimensional (3D) models, which can replicate physiological conditions, for investigating pathological mechanisms leading to visual loss. This review provides an overview of the most common retinal diseases, relating to in vivo models, with a specific focus on alternative 2D and 3D in vitro models that can replicate the different cellular and matrix components of retinal layers, as well as injury insults that induce retinal disease and loss of the visual function.

scholarly journals Pre-Clinical In Vitro Models Used in Cancer Research: Results of a Worldwide Survey

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6033
Author(s):  
Sarai Martinez-Pacheco ◽  
Lorraine O’Driscoll
Keyword(s):  
Cancer Research ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Cost Effective ◽  
Cell Types ◽  
3D Models ◽  
In Vitro Models ◽  
3D Cultures

To develop and subsequently get cancer researchers to use organotypic three-dimensional (3D) models that can recapitulate the complexity of human in vivo tumors in an in vitro setting, it is important to establish what in vitro model(s) researchers are currently using and the reasons why. Thus, we developed a survey on this topic, obtained ethics approval, and circulated it throughout the world. The survey was completed by 101 researchers, across all career stages, in academia, clinical or industry settings. It included 40 questions, many with multiple options. Respondents reported on their field of cancer research; type of cancers studied; use of two-dimensional (2D)/monolayer, 2.5D and/or 3D cultures; if using co-cultures, the cell types(s) they co-culture; if using 3D cultures, whether these involve culturing the cells in a particular way to generate spheroids, or if they use additional supports/scaffolds; techniques used to analyze the 2D/2.5D/3D; and their downstream applications. Most researchers (>66%) only use 2D cultures, mainly due to lack of experience and costs. Despite most cancer researchers currently not using the 3D format, >80% recognize their importance and would like to progress to using 3D models. This suggests an urgent need to standardize reliable, robust, reproducible methods for establishing cost-effective 3D cell culture models and their subsequent characterization.

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