Cell Line Culture in Pharmaceutical Development and Application: A Review (original) (raw)
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Cell Lines for Drug Discovery and Development - a Review
2021
Generally, cell culture, involves utilization of a suspension or a stationary media, which results in the development of cells in an outside atmosphere with suitable conditions. On the other hand, enzymatic action is employed to attain cells for culture, which is the mechanical disaggregation process that is mostly chosen given that the methods give a simpler and less distressing way of achieving cells. The technique involves the segmentation of a tissue into slighter pieces from which the splinted cells is then gathered. On the other hand, primary explants systems can be utilized to attain the cells. Though, this process is principally helpful for the disaggregation of lesser amounts of tissue. Therefore, with the application of animal cell culture methods the utilization of animals in scientific trials will be considerably diminished. The current review mainly focuses in giving a substitute to animal testing by developing cells in a plate and is a feasible means to substitute anim...
Cell Lines as In Vitro Models for Drug Screening and Toxicity Studies
Drug Development and Industrial Pharmacy, 2005
Cell culture is highly desirable, as it provides systems for ready, direct access and evaluation of tissues. The use of tissue culture is a valuable tool to study problems of clinical relevance, especially those related to diseases, screening, and studies of cell toxicity mechanisms. Ready access to the cells provides the possibility for easy studies of cellular mechanisms that may suggest new potential drug targets and, in the case of pathological-derived tissue, it has an interesting application in the evaluation of therapeutic agents that potentially may treat the dysfunction. However, special considerations must be addressed to establish stable in vitro function. In primary culture, these factors are primarily linked to greater demands of tissue to adequately survive and develop differentiated conditions in vitro. Additional requirements include the use of special substrates (collagen, laminin, extracellular matrix preparations, etc.), growth factors and soluble media supplements, some of which can be quite complex in their composition. These demands, along with difficulties in obtaining adequate tissue amounts, have prompted interest in developing immortalized cell lines which can provide unlimited tissue amounts. However, cell lines tend to exhibit problems in stability and/ or viability, though they serve as a feasible alternative, especially regarding new potential applications in cell transplant therapy. In this regard, stem cells may also be a source for the generation of various cell types in vitro. This review will address aspects of cell culture system application, with focus on immortalized cell lines, in studying cell function and dysfunction with the primary aim being to identify cell targets for drug screening.
Cell Culture Technology for Pharmaceutical and Cell-Based Therapies S. Ozturk and Hu WS copy
International Standard Book Number-10: 0-8247-5334-8 (Hardcover) International Standard Book This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use.
Three-dimensional cell cultures as a new tool in drug discovery
Periodicum Biologorum, 2016
Background and purpose: Producing of reliable information about pharmacological activity of new chemical entities is essential in early stages of drug discovery and development. There is a continuous need for improvement of existing in vitro technologies, in order to get more accurate and more predictive biological data (and for compounds selection) in pre-clinical screening methods and models. Materials and methods: Two-dimensional (2D) cell cultures, in comparison with original tissues, does not fully reproduce in vivo cell growth and differentiation. Therefore, significant efforts have been made toward the development of more realistic three-dimensional (3D) in vitro cell culture models that would better mimic tissue physiology. Results: Two-dimensional (2D) cell cultures, in comparison with original tissues, does not fully reproduce in vivo cell growth and differentiation. Therefore, significant efforts have been made toward the development of more realistic three-dimensional (3D) in vitro cell culture models that would better mimic tissue physiology. Basic concepts and advantages of 3D cell cultures, as well as different approaches in technologies that enable the cell growth in 3D will be presented here. Possible applications of 3D cell culture in drug discovery will be discussed, and example of formation of spherical growth of three different human breast cancer cells (MDA-MB-231, SK-BR-3 and T-47D cells) in 3D format will be shown. Conclusions: Although biological significance of obtained data from 2D and 3D cell cultures is still poorly understood, discrepancy of compunds activity illustrated importance of implementation 3D cell culture assays in early part of drug discovery process.
Two-Dimensional (2D) and Three-Dimensional (3D) Cell Culturing in Drug Discovery
Cell Culture, 2019
Cell culture is an indispensable in vitro tool used to improve our perception and understanding of cell biology, the development of tissue engineering, tissue morphology, mechanisms of diseases and drug action. Efficient cell culturing techniques both in vitro and in vivo allow researchers to design and develop new drugs in preclinical studies. Two-dimensional (2D) cell cultures have been used since 1900s and are still a dominant method in many biological studies. However, 2D cell cultures poorly imitate the conditions in vivo. Recently three-dimensional (3D) cell cultures have received remarkable attention in studies such as drug discovery and development. Optimization of cell culture conditions is very critical in ensuring powerful experimental reproducibility, which may help to find new therapies for cancer and other diseases. In this chapter, we discuss the 2D and 3D cell culture technologies and their role in drug discovery.
Biological & Pharmaceutical Bulletin, 2004
Selection of drug candidates that are highly permeable across human intestinal epithelium and resistant to first-pass metabolism is an important step in oral drug development. In vitro permeation assays with cultured enterocyte-like cells are routinely used in the pharmaceutical industry for the prediction of human intestinal absorption in the early drug discovery process. 1-4) Cultured Caco-2 cells are described in the literature as the reference model to study intestinal drug absorption. The parental Caco-2 cell line exhibits characteristics close to epithelial cells from ileum in spite of their colonic origin. Engle et al. 5) indicate that the parental Caco-2 cell line heterogeneously differentiates due to different cell populations (enterocytes and colonocytes) present in the same culture. In addition, the cytochrome 3A family, responsible for metabolism of more than 50% of orally administered drugs, is lacking in the parental cell line which has limits its application. 6,7) Different authors reported that the Caco-2 clone TC7 cell line, obtained from high passages, is a suitable model for the evaluation of the role of small intestine in the absorption and biotransformation of drugs by displaying, (i) higher taurocholic acid transport activity, (ii) higher brush-border associated hydrolase sucrase-isomaltase activity, and (iii) higher cytochrome 3A activity. 6-8) In addition, high potential for rank ordering compounds and prediction of human intestinal absorption was found using the TC7 clone. 4) However, the differentiation of Caco-2 cells required a long culture period (21-d) with daily medium change. 4,9) Accelerated in vitro Caco-2 permeation assays were devel-1986
The use of bioreactors as in vitro models in pharmaceutical research
Drug Discovery Today, 2013
Bringing a new drug to market is costly in terms of capital and time investments, and any development issues encountered during late-stage clinical trials can often be the result of in vitro-in vivo extrapolations (IVIVE) not accurately reflecting clinical outcome. In the discipline of drug metabolism and pharmacokinetics (DMPK), current in vitro cellular methods do not provide the 3D structure and function of organs found in vivo; therefore, new dynamic methods need to be established to aid improvement of IVIVE. In this review, we highlight the importance of model progression into dynamic systems for use within drug development, focusing on devices developed currently in the areas of the liver and bloodbrain barrier (BBB), and the potential to develop models for other organ systems, such as the kidney.
Application of Caco-2 cell line in herb-drug interaction studies: current approaches and challenges
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques, 2014
The Caco-2 model is employed in pre-clinical investigations to predict the likely gastrointestinal permeability of drugs because it expresses cytochrome P450 enzymes, transporters, microvilli and enterocytes of identical characteristics to the human small intestine. The FDA recommends this model as integral component of the Biopharmaceutics Classification System (BCS). Most dedicated laboratories use the Caco-2 cell line to screen new chemical entities through prediction of its solubility, bioavailability and the possibility of drug-drug or herb-drug interactions in the gut lumen. However, challenges in the inherent characteristics of Caco-2 cell and inter-laboratory protocol variations have resulted to generation of irreproducible data. These limitations affect the extrapolation of data from pre-clinical research to clinical studies involving drug-drug and herb-drug interactions. This review addresses some of these caveats and enumerates the plausible current and future approaches ...