Abstract：
:The selection of drug candidates early in development has become increasingly important to minimize the use of animals and to avoid costly failures of drugs later in development. In vitro systems to predict and assess organ toxicity have so far been of limited value due to difficulties in demonstrating in vivo-relevant toxicity at a cell culture level. To overcome the limitations of single-cell type monolayer cultures and short-lived primary cell preparations, researchers have created novel 3-dimensional culture systems which appear to more closely resemble in vivo biology. These could become a key for the pharmaceutical industry in the evaluation of drug candidates. However, the value and acceptance of those new models in standard drug safety applications have yet to be demonstrated. This review aims to provide an overview of the different approaches undertaken in the field of pre-clinical safety assessment, organ toxicity, in particular, with an emphasis on examples and technical challenges.
journal_name
Adv Drug Deliv Revjournal_title
Advanced drug delivery reviewsauthors
Roth A,Singer Tdoi
10.1016/j.addr.2013.12.005subject
Has Abstractpub_date
2014-04-01 00:00:00pages
179-89eissn
0169-409Xissn
1872-8294pii
S0169-409X(13)00291-3journal_volume
69-70pub_type
杂志文章,评审abstract：:Modern pharmaceutical delivery systems are intended to produce plasma drug concentration versus time profiles that result in optimum therapeutic efficacy and a minimum of drug concentration-dependent adverse effects. To accomplish this requires that the drug delivery rate and temporal profile be based on the pharmacok...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章
doi：10.1016/s0169-409x(98)00028-3
更新日期：1998-09-07 00:00:00
abstract：:The blood-brain barrier (BBB) is a highly regulated and efficient barrier that provides a sanctuary to the brain. It is designed to regulate brain homeostasis and to permit selective transport of molecules that are essential for brain function. Unfortunately, drug transport to the brain is hampered by this almost impe...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2011.11.010
更新日期：2012-05-15 00:00:00
abstract：:Among non-viral vectors, chitosan and chitosan derivatives have been developed in vitro and in vivo for DNA and siRNA delivery systems because of their cationic charge, biodegradability and biocompatibility, as well as their mucoadhesive and permeability-enhancing properties. However, the transfection efficiency of ch...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2009.08.004
更新日期：2010-01-31 00:00:00
abstract：:miRNA-based technologies provide attractive tools for several liver tissue engineering approaches. Herein, we review the current state of miRNA applications in liver tissue engineering. Several miRNAs have been implicated in hepatic disease and proper hepatocyte function. However, the clinical translation of these fin...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2015.06.005
更新日期：2015-07-01 00:00:00
abstract：:We review the early developments in drug delivery from 1960 to 1990 with emphasis on the fundamental aspects of the field and how they shaped the collaboration of pharmaceutical scientists, chemists, biologists, engineers and medical scientists towards the development of advanced drug delivery systems. Emphasis is giv...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2012.09.040
更新日期：2013-01-01 00:00:00
abstract：:Theranostic systems support diagnostic and therapeutic functions in a single integrated entity and enable precise spatiotemporal control of the generation of therapeutic molecules according to the individual patient's disease state, thereby maximizing the therapeutic outcome and minimizing side effects. These systems ...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2016.05.006
更新日期：2016-10-01 00:00:00
abstract：:Peptide nucleic acid (PNA) is a DNA mimic having a pseudopeptide backbone that makes it extremely stable in biological fluids. PNA binds complementary RNA and DNA with high affinity and specificity. These qualities make PNA a leading agent among "third generation" antisense and antigene agents. Unfortunately, fast pro...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(02)00182-5
更新日期：2003-02-10 00:00:00
abstract：:Hydrogels prepared via self-assembly offer scalable and tunable platforms for drug delivery applications. Molecular-scale self-assembly leverages an interplay of attractive and repulsive forces; drugs and other active molecules can be incorporated into such materials by partitioning in hydrophobic domains, affinity-me...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2021.01.006
更新日期：2021-01-12 00:00:00
abstract：:Intravenous administration of low (milligram) doses of nanoparticulate materials in pigs can lead to acute cardiopulmonary, hemodynamic, hematological, biochemical and dermatological changes within minutes, mimicking the human infusion (or anaphylactoid) reactions to many state-of-the-art (nano)medicines and biologica...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2012.07.005
更新日期：2012-12-01 00:00:00
abstract：:The future of non-viral gene therapy depends on a detailed understanding of the barriers to delivery of polynucleotides. These include physicomechanical barriers, which limit the design of delivery devices, physicochemical barriers that influence self-assembly of colloidal particulate formulations, and biological barr...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(00)00133-2
更新日期：2001-03-01 00:00:00
abstract：:Current treatment of human immunodeficiency virus type-1 (HIV-1) infection involves a combination of antiretroviral drugs (ARVs) that target different stages of the HIV-1 life cycle. This strategy is commonly referred to as highly active antiretroviral therapy (HAART) or combined antiretroviral therapy (cART). Membran...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2016.05.001
更新日期：2016-08-01 00:00:00
abstract：:Transdermal and rectal routes of drugs are very important as a useful supplement of oral routes and the direct exposing method of drugs when the systemic and local effects are required. The widespread use of parent cyclodextrins (CDs) and chemically modified CD derivatives (CD derivatives) for in-vitro and in-vivo der...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章
doi：10.1016/s0169-409x(98)00056-8
更新日期：1999-03-01 00:00:00
abstract：:A recombinant C-terminal truncated form of the human soluble tumor necrosis factor receptor type I (sTNF-RI) was produced in E. coli. This soluble receptor contains the first 2.6 of the 4 domains of the intact sTNF-RI molecule. A monoPEGylated form of this molecule was produced using a 30 kD methoxyPEG aldehyde with a...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(03)00112-1
更新日期：2003-09-26 00:00:00
abstract：:Amorphisation of poorly water-soluble drugs is one approach that can be applied to improve their solubility and thus their bioavailability. Amorphisation is a process that usually requires deliberate external energy input. However, amorphisation can happen both unintentionally, as in process-induced amorphisation duri...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2015.12.014
更新日期：2016-05-01 00:00:00
abstract：:Immunotherapy has been widely explored for applications to both augment and suppress intrinsic host immunity. Clinical achievements have seen a number of immunotherapeutic drugs displace established strategies like chemotherapy in treating immune-associated diseases. However, single drug approaches modulating an indiv...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2017.05.013
更新日期：2017-05-15 00:00:00
abstract：:In the past 15years, despite that regenerative medicine has shown great potential for cardiovascular diseases, the outcome and safety of stem cell transplantation has shown controversial results in the published literature. Medical imaging might be useful for monitoring and quantifying transplanted cells within the he...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2017.07.012
更新日期：2017-10-01 00:00:00
abstract：:Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pat...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2018.04.008
更新日期：2018-03-01 00:00:00
abstract：:We have entered a new era in understanding CNS circuitry involved in acute and chronic pain. The ability to objectively measure a pain or analgesic state of the brain using non-invasive methods that define neural activation provides the possibility for top-down approaches to drug discovery. These brain maps represent ...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(03)00099-1
更新日期：2003-08-28 00:00:00
abstract：:Successfully translating anti-cancer nanomedicines from pre-clinical proof of concept to demonstration of therapeutic value in the clinic is challenging. Having made significant advances with drug delivery technologies, we must learn from other areas of oncology drug development, where patient stratification and targe...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2016.04.025
更新日期：2017-01-01 00:00:00
abstract：:Cytochrome P450 enzymes (CYPs) form one of the most important enzyme families involved in the metabolism of xenobiotics. CYPs comprise many isoforms, which catalyze a wide variety of reactions, and potentially, a large number of different metabolites can be formed. However, it is often hard to rationalize what metabol...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2015.04.020
更新日期：2015-06-23 00:00:00
abstract：:Systemic drug delivery methods such as oral or parenteral administration of free drugs possess relatively low treatment efficiency and marked adverse side effects. The use of nanoparticles for drug delivery in most cases substantially enhances drug efficacy, improves pharmacokinetics and drug release and limits their ...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2019.07.010
更新日期：2019-04-01 00:00:00
abstract：:Ultrasound (US) imaging is an exquisite tool for the non-invasive and real-time diagnosis of many different diseases. In this context, US contrast agents can improve lesion delineation, characterization and therapy response evaluation. US contrast agents are usually micrometer-sized gas bubbles, stabilized with soft o...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2013.11.013
更新日期：2014-06-01 00:00:00
abstract：:Despite advances in medicine and biomedical sciences, cancer still remains a major health issue. Complex interactions between tumors and their microenvironment contribute to tumor initiation and progression and also contribute to the development of drug resistant tumor cell populations. The complexity and heterogeneit...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2014.07.002
更新日期：2014-12-15 00:00:00
abstract：:Micro-/nanoscale technologies such as lithographic techniques and microfluidics offer promising avenues to revolutionalize the fields of tissue engineering, drug discovery, diagnostics and personalized medicine. Microfabrication techniques are being explored for drug delivery applications due to their ability to combi...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2011.11.013
更新日期：2012-05-01 00:00:00
abstract：:Injury to the podocytes is the initiating cause of many renal diseases, leading to proteinuria with possible progression to end-stage renal disease. Podocytes are highly specialized cells, with an important role in maintaining the glomerular filtration barrier and producing growth factors for both mesangial cells and ...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2010.08.012
更新日期：2010-11-30 00:00:00
abstract：:Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described. In the discovery setting 'the rule of 5' predicts that poor absorption or permeation is more likely when there are more than 5 H-bond donors, 10 H-bond acceptors, the molecular weight ...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(00)00129-0
更新日期：2001-03-01 00:00:00
abstract：:DNA plasmid-based gene expression systems are being widely investigated for the potential treatment of genetic and acquired disease and for DNA-based vaccination. A number of human clinical trials are in progress using plasmid-based drugs. The regulatory framework that has been applied to biologicals such as recombina...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章
doi：10.1016/s0169-409x(97)00105-1
更新日期：1998-03-02 00:00:00
abstract：:Gene and antisense/ribozyme therapy possesses tremendous potential for the successful treatment of genetically based diseases, such as cancer. Several cancer gene therapy strategies have already been realized in vitro, as well as in vivo. A few have even reached the stage of clinical trials, most of them phase I, whil...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(02)00046-7
更新日期：2002-09-13 00:00:00
abstract：:Nuclear import of macromolecules or particles is a strictly regulated phenomenon that is now understood in some depth at the molecular level. Transport across nuclear membranes is controlled by nuclear pores, with the involvement of cytoplasmic receptors and accessory molecules. Each nuclear pore complex is an assembl...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章
doi：10.1016/s0169-409x(98)00050-7
更新日期：1998-10-05 00:00:00
abstract：:There is an urgent need for new strategies to combat infectious diseases in developing countries. Many pathogens have evolved to elude immunity and this has limited the utility of current therapies. Additionally, the emergence of co-infections and drug resistant pathogens has increased the need for advanced therapeuti...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2009.11.011
更新日期：2010-03-18 00:00:00
