Current Pharmaceutical Biotechnology - Volume 21, Issue 9, 2020

In 1791, Galvani established that electricity activated excitable cells. In the two centuries that followed, electrode stimulation of neuronal, skeletal and cardiac muscle became the adjunctive method of choice in experimental, electrophysiological, and clinical arenas. This approach underpins breakthrough technologies like implantable cardiac pacemakers that we currently take for granted. However, the contact dependence, Read More

Growing evidence suggests that Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) can be used as a new human cell-based platform to assess cardiac toxicity/safety during drug development. Cardiotoxicity assessment is highly challenging due to species differences and various toxicities, such as electrophysiological and contractile toxicities, which can result in proarrhythmia and heart fail Read More

Human hepatocytes are essential cell types for pharmacokinetics and the safety evaluation of pharmaceuticals. However, widely used primary hepatocytes with individual variations in liver function lose those functions rapidly in culture. Hepatic cell lines are convenient to use but have low liver functions. Human-Induced Pluripotent Stem (hiPS) cells can be expanded and potentially differentiated into any cell or tissue, includ Read More

Neurotoxicity, as well as cardiotoxicity and hepatotoxicity, resulting from administration of a test article is considered a major adverse effect both pre-clinically and clinically. Among the different types of neurotoxicity occurring during the drug development process, seizure is one of the most serious one. Seizure occurrence is usually assessed using in vivo animal models, the Functional Observational Battery, the Irwin test or e Read More

In preclinical drug development, accurate prediction of drug effects on the human heart is critically important, whether in the context of cardiovascular safety or for the purpose of modulating cardiac function to treat heart disease. Current strategies have significant limitations, whereby, cardiotoxic drugs can escape detection or potential life-saving therapies are abandoned due to false positive toxicity signals. T Read More

Drug-induced toxicity remains one of the leading causes of discontinuation of the drug candidate and post-marketing withdrawal. Thus, early identification of the drug candidates with the potential for toxicity is crucial in the drug development process. With the recent discovery of human- Induced Pluripotent Stem Cells (iPSC) and the establishment of the differentiation protocol of human iPSC into the cell types of interest, t Read More

Current cardiac safety assessment platforms (in vitro hERG-centric, APD, and/or in vivo animal QT assays) are not fully predictive of drug-induced Torsades de Pointes (TdP) and do not address other mechanism-based arrhythmia, including ventricular tachycardia or ventricular fibrillation, or cardiac safety liabilities such as contractile and structural cardiotoxicity which are another growing safety concerns. We organized the C Read More

Background: Estrogen Receptors (ER) are members of the nuclear intracellular receptors family. ER once activated by estrogen, it binds to DNA via translocating into the nucleus and regulates the activity of various genes. Withaferin A (WA) - an active compound of a medicinal plant Withania somnifera was reported to be a very effective anti-cancer agent and some of the recent studies has demonstrated that WA is capable of Read More

Aims: Biodegradable polymeric microneedles containing atorvastatin calcium were developed in order to improve the percutaneous absorption of the drug, useful for the treatment of hypercholesterolemia. Background: The use of physical enhancers like microneedles have shown good results to increase the delivery of drugs through the skin, the use of microneedles has very important advantages for transdermal drug delivery Read More

Background and Objective: Dental peri-implantitis, which can be caused by several different microbial factors, is characterized by inflammatory lesions of the surrounding hard and soft tissues of an oral implant. Matrix Metalloproteinase 9 (MMP9) is thought to be involved in the pathogenesis of peri-implantitis. However, the regulatory mechanism of MMP9 in peri-implantitis has not been fully elucidated. In this study, we tried t Read More

Objective: Amylases enzymes hydrolyze starch molecules to produce diverse products including dextrins, and progressively smaller polymers. These include glucose units linked through α-1- 1, α-1-4, α-1-6, glycosidic bonds. Methods: This enzyme carrying an (α /β) 8 or TIM barrel structure is also produced containing the catalytic site residues. These groups of enzymes possess four conserved regions in their primary sequen Read More