Abstract:
:In drug development, in vitro human model systems are absolutely essential prior to the clinical trials, considering the increasing number of chemical compounds in need of testing, and, keeping in mind that animals cannot predict all the adverse human health effects and reactions, due to the species-specific differences in metabolic pathways. The liver plays a central role in the clearance and biotransformation of chemicals and xenobiotics. In vitro liver model systems by using highly differentiated human cells could have a great impact in preclinical trials. Membrane biohybrid systems constituted of human hepatocytes and micro- and nano-structured membranes, represent valuable tools for studying drug metabolism and toxicity. Membranes act as an extracellular matrix for the adhesion of hepatocytes, and compartmentalise them in a well-defined physical and chemical microenvironment with high selectivity. Advanced 3-D tissue cultures are furthermore achieved by using membrane bioreactors (MBR), which ensure the continuous perfusion of cells protecting them from shear stress. MBRs with different configurations allow the culturing of cells at high density and under closely monitored high perfusion, similarly to the natural liver. These devices that promote the long-term maintenance and differentiation of primary human hepatocytes with preserved liver specific functions can be employed in drug testing for prolonged exposure to chemical compounds and for assessing repeated-dose toxicity. The use of primary human hepatocytes in MBRs is the only system providing a faster and more cost-effective method of analysis for the prediction of in vitro human drug metabolism and enzyme induction alternative and/or complementary to the animal experimentation. In this paper, in vitro models for studying drug metabolism and toxicity as advanced biohybrid membrane systems and MBRs will be reviewed.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Salerno S,Bartolo Ldoi
10.2174/1381612822666161025155616subject
Has Abstractpub_date
2017-01-01 00:00:00pages
319-327issue
2eissn
1381-6128issn
1873-4286pii
CPD-EPUB-79259journal_volume
23pub_type
杂志文章,评审abstract::Manufacturing of pharmaceutical solids involves different unit operations and processing steps such as powder blending, fluidization, sieving, powder coating, pneumatic conveying and spray drying. During these operations, particles come in contact with other particles, different metallic, glass or polymer surfaces and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666151008124811
更新日期:2015-01-01 00:00:00
abstract::The study of natural sources such as plants, microorganisms and marine organisms has developed interest among the scientific community in recent years for their extensive and diverse chemical composition and consequent biological potential. The search for antitumor compounds is among the lead causes that justify phyto...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190115144241
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abstract:BACKGROUND:The development of appropriate pharmaceutical formulations for routine neonatal practice is challenging because of the developmental characteristics and the need for it to be specifically ageappropriate. This has led to wide use of extemporaneous formulations, which lack standardized procedures that can resu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170926122613
更新日期:2017-01-01 00:00:00
abstract::Over the last years a number of reports have described elevated numbers of regulatory T (Treg) cells inside of tumors, in close proximity of the tumor, draining lymph nodes and also in peripheral blood of patients with solid tumors and hematologic malignancies. There is increasing evidence that Treg cells can migrate ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788453211
更新日期:2009-01-01 00:00:00
abstract::During the last years, mass spectrometry has revolutionised protein biochemistry and has advanced to a superior tool for the identification and detailed analysis of peptides and proteins. The high throughput allowed by some mass spectrometry platforms has enabled the important step from analysis of individual proteins...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054546932
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abstract::Biochemical biomarkers are important candidates for the diagnosis and prognosis of neurological diseases of autoimmune etiology, since they may reflect the presence, nature and intensity of certain immune responses caused by both genetic and environmental processes. Different body fluids such as cerebrospinal fluid (C...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802502143
更新日期:2012-01-01 00:00:00
abstract::There is growing evidence for the involvement of glutamatergic abnormalities in schizophrenia. Uncompetitive NMDA receptor (NMDAR) antagonists induce effects closely resembling both the positive and negative symptoms of schizophrenia; candidate risk genes for schizophrenia converge on the NMDAR expressing synapse; and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788957438
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abstract::The present review discusses the mechanism of late stent thrombosis and its distinction from restenosis and summarizes the advisory note issued by FDA on the proper usage of different treatments available for atherosclerosis. In light of the latest developments, a plethora of new stents have been and continue to be de...
journal_title:Current pharmaceutical design
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abstract::Glioblastoma (GBM) is a deadly tumor, which in spite of surgery and radio/chemotherapy frequently undergoes relapses related to the infiltration of the normal parenchyma and to resistance to cytotoxic and radiation therapy. Immunotherapy may represent a promising approach, which may complement existing therapies with ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797249206
更新日期:2011-01-01 00:00:00
abstract::Low density lipoproteins (LDL) and high density lipoproteins (HDL) are independent risk factors for coronary heart disease (CHD); decreasing LDL-cholesterol (LDL-C) levels with statin therapy represents the primary goal in the management of cardiovascular disease. However, despite the efficacy of statins in reducing c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990298
更新日期:2013-01-01 00:00:00
abstract::The treatment of skin wounds represents an important research area due to the important physiological and aesthetic role of this tissue. During the last years, nanoparticles have emerged as important platforms to treat skin wounds. Silver, gold, and copper nanoparticles, as well as titanium and zinc oxide nanoparticle...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150901104601
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Cyclodextrins (CDs), as one type of the novel pharmaceutical excipients, have been widely used in drug delivery and pharmaceutical industry. Over the past decades, a large amount of molecular modeling studies in CDs were reported for profound understanding of structural, dynamic and energetic features of CDs...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161208142617
更新日期:2017-01-01 00:00:00
abstract::Phase-change contrast agents (PCCAs) for ultrasound-based applications have resulted in novel ways of approaching diagnostic and therapeutic techniques beyond what is possible with microbubble contrast agents and liquid emulsions. When subjected to sufficient pressures delivered by an ultrasound transducer, stabilized...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212800099883
更新日期:2012-01-01 00:00:00
abstract::Diabetic macular edema (DME) represents the most common cause of vision loss in patients affected by diabetes mellitus. Although the pathophysiology of DME is not wholly understood, vascular endothelial growth factor (VEGF) has been identified as a key contributor to the development of DME. In addition, latest informa...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150909095756
更新日期:2015-01-01 00:00:00
abstract::The gut microbiota plays significant roles in the human body during all spheres' of life and influences innate immunity, promotes granulocyte signaling and provides resistance during pathogenic colonization of the gut; crucial for a healthy life. Antibiotics directly affect the gut microbiota that consequently alters ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666171227221731
更新日期:2018-01-01 00:00:00
abstract::Neglected parasitic diseases are a group of infections currently considered as a worldwide concern. This fact can be attributed to the migration of these diseases to developed and developing countries, associated with therapeutic insufficiency resulted from the low investment in the research and development of new dru...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200701160904
更新日期:2020-01-01 00:00:00
abstract::Obesity was first described as a low-grade inflammatory condition more than a decade ago. However, it is only relatively recently that obese individuals have been described with increased macrophage infiltration of adipose tissue, as well as an increase in the number of "M1" or "classically activated" macrophages. Fur...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784246153
更新日期:2008-01-01 00:00:00
abstract::The purpose of this study is to answer the following question: What are the typical features of abnormal bodily experiences (ABEs) in persons affected by acute first-episode schizophrenia? Our overall objective is to contribute to enhance early diagnosis of schizophrenia, and providing supplementary diagnostic criteri...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212799316181
更新日期:2012-01-01 00:00:00
abstract::Neuropathic pain is characterized by complicated combination of positive (e.g., hyperalgesia and allodynia) and negative (e.g., hypoesthesia and hypoalgesia) symptoms, and is often refractory to conventional pharmacological agents, including morphine. Although the molecular mechanisms for positive symptoms are extensi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666141027113923
更新日期:2015-01-01 00:00:00
abstract::Cardiovascular disease remains the number one killer in the United States and many other countries. Each year, there are enormous research efforts on its pathogenesis, prevention and treatment led by scientists worldwide. One of the most significant research areas is the impact and mechanisms of existing or new cardio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113196660744
更新日期:2014-01-01 00:00:00
abstract::Protozoan parasites, such as those responsible for malaria and African Sleeping Sickness, represent a huge burden to the developing world. Current chemotherapy to combat these diseases is inadequate: antiquated, toxic and increasingly ineffective due to drug resistance. In this article, the potential usefulness of tar...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784041042
更新日期:2008-01-01 00:00:00
abstract::The cardiovascular system exhibits significant daily rhythms in physiologic processes (heart rate, blood pressure, cardiac contractility and function), and molecular gene and protein expression. An increasing number of clinical and experimental studies demonstrate the circadian system is an important underlying mechan...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150706105926
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:There is a strong rationale for usage of anti-angiogenic agents in epithelial ovarian cancer. Bevacizumab is the most widely investigated anti-VEGF agent and has shown promising results in recent clinical trials. OBJECTIVE:To review the rationale and usage of bevacizumab in advanced epithelial ovarian cance...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212802002689
更新日期:2012-01-01 00:00:00
abstract::Aspirin is the cornerstone of treatment in patients with coronary artery disease. However, several studies investigating the in vitro response of platelets to the administration of aspirin showed this response to be variable, with some patients exhibiting non-responsiveness or resistance. Aspirin resistance may be cat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787846964
更新日期:2009-01-01 00:00:00
abstract::Type 2 diabetes is associated with substantially increased cardiovascular mortality. The need to reduce the progression of atherosclerosis alongside lowering blood glucose levels is now well established. Ideally, pharmaceutical treatment should address both of these needs. This review summarises current evidence of th...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789057995
更新日期:2009-01-01 00:00:00
abstract::1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE- PEG) is a widely used phospholipids-polymer conjugate in drug delivery applications. It is a biocompatible, biodegradable and amphiphilic material which can also be functionalized with various biomolecules for specific functions. With the em...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150115144003
更新日期:2015-01-01 00:00:00
abstract::Agitation is commonly seen in acute schizophrenic patients and core symptoms include a wide range of symptom. It requires rapid and effective treatment approaches in order to protect patient and caregiver from potential injury. Clinician's decision of pharmacological treatment should be individualized to the needs and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2005-01-01 00:00:00
abstract::We set up two models of gastric bleeding in rats using low-dose aspirin (ASA) and the antiplatelet drug clopidogrel, a P2Y₁₂ receptor antagonist, and examined the effect of antiulcer drugs on gastric bleeding and ulcerogenic responses under such conditions. Under urethane anesthesia, two catheters were inserted into t...
journal_title:Current pharmaceutical design
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doi:10.2174/13816128113199990418
更新日期:2014-01-01 00:00:00
abstract::Guanine-rich sequences found in telomeres and oncogene promoters have the ability to form G-quadruplex structures. In this paper we describe the use of a virtual screening assay to search a database of FDA-approved compounds for compounds with the potential to bind G-quadruplex DNA. More than 750 telomerase inhibitors...
journal_title:Current pharmaceutical design
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更新日期:2013-01-01 00:00:00
abstract::Protein-protein interactions (PPI) are involved in vital cellular processes and are therefore associated to a growing number of diseases. But working with them as therapeutic targets comes with some major hurdles that require substantial mutations from our way to design drugs on historical targets such as enzymes and ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802651571
更新日期:2012-01-01 00:00:00