Abstract：
:Although the oral route is the most popular and acceptable way of drug administration owing to good patient compliance and safety, oral drug delivery is faced with continuous challenges regarding poorly soluble, poorly permeable or gastrointestinally unstable drugs such as proteins and polypeptides. The overall bioavailability and therapeutic effect still needs to be further improved by innovative delivery technologies. Recently, various novel strategies, for instance using ligand-decorated carriers, have been investigated for delivery of poorly absorptive therapeutics orally. In this review, we will discuss the state of the art of ligand-mediated targeting to intestinal epithelia for oral delivery of drugs with low bioavailability.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Zhang X,Wu Wdoi
10.1016/j.drudis.2014.03.001subject
Has Abstractpub_date
2014-07-01 00:00:00pages
898-904issue
7eissn
1359-6446issn
1878-5832pii
S1359-6446(14)00078-6journal_volume
19pub_type
杂志文章,评审abstract：:Many pharmaceutical companies aim to reduce reactive metabolite formation by chemical modification at early stages of drug discovery. A practice often applied is the detection of stable trapping products of electrophilic intermediates with nucleophilic trapping reagents to guide rational structure-based drug design. T...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.11.018
更新日期：2017-05-01 00:00:00
abstract：:Kidneys have a major role in normal physiology and metabolic homeostasis. Loss or impairment of kidney function is a common occurrence in several metabolic disorders, including hypertension and diabetes. Chronic kidney disease (CKD) affect nearly 10% of the population worldwide; ranks 18th in the list of causes of dea...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.04.020
更新日期：2017-07-01 00:00:00
abstract：:Corneal blindness caused by limbal stem cell deficiency (LSCD) is a prevailing disorder worldwide. Clinical outcomes for LSCD therapy using amniotic membrane (AM) are unpredictable. Hydrogels can eliminate limitations of standard therapy for LSCD, because they present all the advantages of AM (i.e. biocompatibility, i...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.07.012
更新日期：2013-01-01 00:00:00
abstract：:The research and development (R&D) of new drugs indicates scientific progress and economic development. However, little is known regarding ongoing or recent clinical trials in China. We analyzed data from clinical trials published before December 31, 2019, and found that the annual registration numbers are increasing ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2020.09.030
更新日期：2020-12-01 00:00:00
abstract：:The eye is afflicted by chronic vision debilitating neovascular disorders, such as age-related macular degeneration, proliferative diabetic retinopathy, and corneal angiogenesis. Photodynamic therapy (PDT) is an innovative, evolving approach for treating neovascular diseases of the eye. PDT refers to the process of ac...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.12.005
更新日期：2008-02-01 00:00:00
abstract：:Statins are an established therapeutic modality for the treatment of hypercholesterolemia. Although they generally exhibit a good efficacy and tolerability profile, their reputation has been tarnished as a result of reports of myotoxicity and, more recently, observations of proteinuria. The increased incidence of prot...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.03.017
更新日期：2006-05-01 00:00:00
abstract：:Our understanding of the detailed recognition and processing of clinically useful therapeutic agents has grown rapidly in recent years, and we are now able to begin to apply this knowledge to the rational treatment of disease. Mammalian carboxylesterases (CEs) are enzymes with broad substrate specificities that have k...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03383-0
更新日期：2005-03-01 00:00:00
abstract：:In therapeutic areas aimed at developing an orally administered drug, the pharmacokinetic profile of a drug candidate after oral administration in vivo is pivotal in evaluating its success. This can be done by monitoring the plasma concentration versus time after dosing and calculating the area under the curve (AUC). ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(98)01299-9
更新日期：1999-05-01 00:00:00
abstract：:Proline-rich Akt substrate 40kDa (PRAS40) bridges cell signaling between protein kinase B (Akt) and the mammalian target of rapamycin complex 1 (mTORC1). Both Akt and mTORC1 can phosphorylate PRAS40. As a negative regulator of mTORC1, PRAS40 prevents the binding of mTOR to its substrates. The phosphorylation of PRAS40...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.04.005
更新日期：2016-08-01 00:00:00
abstract：:Decisions in drug development are made on the basis of determinations of cause and effect from experimental observations that span drug development phases. Despite advances in our powers of observation, the ability to determine compound mechanisms from large-scale multi-omic technologies continues to be a major bottle...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2007.10.001
更新日期：2007-11-01 00:00:00
abstract：:Angiogenesis is an exquisitely regulated process that is required for physiological processes and is also important in numerous diseases. Tumors utilize angiogenesis to generate the vascular network needed to supply the cancer cells with nutrients and oxygen, and many cancer drugs aim to inhibit tumor angiogenesis. An...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.09.026
更新日期：2015-02-01 00:00:00
abstract：:Magnetic nanoparticles (MNPs) play a vital role for improved imaging applications. Recently, a number of studies demonstrate MNPs can be applied for targeted delivery, sustained release of therapeutics, and hyperthermia. Based on stable particle size and shape, biocompatibility, and inherent contrast enhancement chara...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.04.018
更新日期：2017-08-01 00:00:00
abstract：:Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte-derived skin tumor. It is the second-most-common cancer affecting the Caucasian population and is responsible for >20% of all skin-cancer-related deaths. The estimated incidence of non-melanoma skin cancer in the USA is >1000000 cases per year, of which roughl...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.01.023
更新日期：2018-04-01 00:00:00
abstract：:The potential of peptide and protein anticancer agents has yet to be realized owing to the many unresolved problems concerning their delivery to the site of a tumor and into tumor cells. However, our understanding of the mechanisms underlying the biological fate and biodistribution of protein and peptide drugs has adv...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(03)02623-0
更新日期：2003-03-15 00:00:00
abstract：:For drug discovery, historical experience is always of significance. Through examining the history of traditional medicines, we find that these medicines have more implications for drug discovery than just providing new chemical entities. The history of traditional medicines indicates that they depended more on the co...
journal_title：Drug discovery today
pub_type： 历史文章,杂志文章
doi：10.1016/j.drudis.2008.07.002
更新日期：2009-02-01 00:00:00
abstract：:The irreversible glycation and oxidation of proteins and lipids produces advanced glycation end products (AGEs). These modified AGEs are triggered to bind the receptor for AGE (RAGE), thereby activating its downstream signaling pathways, such as nuclear factor (NF)-κB and phosphoinositide 3-kinase (PI3K)/Akt, ultimate...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.07.003
更新日期：2020-09-01 00:00:00
abstract：:Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(01)02006-2
更新日期：2001-11-15 00:00:00
abstract：:Quercetin is reported to have numerous pharmacological actions, including antidiabetic, anti-inflammatory and anticancer activities. The main mechanism responsible for its pharmacological activities is its ability to quench reactive oxygen species (ROS) and, hence, decrease the oxidative stress responsible for the dev...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.11.001
更新日期：2020-01-01 00:00:00
abstract：:The clinical advancement of HIV-1 attachment inhibitors was hindered initially by poor bioavailability. Attempts to identify improved candidates revealed that solubility and dissolution-rate-limited absorption are barriers to achieving adequate antiviral plasma levels. This was mitigated by forming nanosized drugs or ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2014.03.025
更新日期：2014-09-01 00:00:00
abstract：:As the field of ocular drug delivery grows so does the potential for novel drug discovery or reformulation in lesser-known diseases of the eye. In particular, rare corneal diseases are an interesting area of research because drug delivery is limited to the outermost tissue of the eye. This review will highlight the op...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.03.005
更新日期：2019-08-01 00:00:00
abstract：:The popularization of genomic high-throughput technologies is causing a revolution in biomedical research and, particularly, is transforming the field of drug discovery. Systems biology offers a framework to understand the extensive human genetic heterogeneity revealed by genomic sequencing in the context of the netwo...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.06.003
更新日期：2014-02-01 00:00:00
abstract：:An overview of drugs approved by FDA in 2016 reveals dramatic disruptions in long-term trends. The number of new molecular entities (NMEs) dropped, reflecting the lowest rate of small-molecule approvals observed in almost five decades. In addition, the pace of industry consolidation slowed substantially. The impact of...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2017.06.011
更新日期：2017-11-01 00:00:00
abstract：:The Science for Life Laboratory Drug Discovery and Development (SciLifeLab DDD) platform reaches out to Swedish academia with an industry-standard infrastructure for academic drug discovery, supported by earmarked funds from the Swedish government. In this review, we describe the build-up and operation of the platform...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.06.026
更新日期：2016-10-01 00:00:00
abstract：:In recent years there has been a dramatic increase in the number of freely accessible online databases serving the chemistry community. The internet provides chemistry data that can be used for data-mining, for computer models, and integration into systems to aid drug discovery. There is however a responsibility to en...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.02.013
更新日期：2012-07-01 00:00:00
abstract：:Drug discovery has historically advanced by synergy and chance. These are proving insufficient to meet the needs of the marketplace and the demands of modern medicine. We describe our strategic approaches to building and employing flexible informatics tools to transform and improve the workflows and efficiencies of th...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(04)03277-5
更新日期：2005-01-01 00:00:00
abstract：:Regenerative approaches are promising avenues to effectively cure diseases rather than merely treating symptoms, but are associated with concerns around proliferation in other organs. Given that targeted delivery holds the promise of delivering a drug precisely to its desired site of action, usually with the prospect ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.12.004
更新日期：2017-06-01 00:00:00
abstract：:The intestinal epithelium is the main barrier restricting the oral delivery of low-permeability drugs. Over recent years, numerous nanocarriers have been designed to improve the efficiency of oral drug delivery. However, the intracellular processes determining the transport of nanocarriers across the intestinal epithe...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.04.007
更新日期：2016-05-01 00:00:00
abstract：:Options for disease-modifying therapies in multiple sclerosis have increased over the past two decades. Among these innovations are interferon-β, glatiramer acetate, fumaric acid and dihydroorotate dehydrogenase inhibitors, an antibody targeting the migration of immune cells, a compound that traps immune cells in lymp...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.11.022
更新日期：2020-11-25 00:00:00
abstract：:The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are ligand-activated nuclear receptors (NRs) that are notorious for their role in drug metabolism, causing unintended drug-drug interactions and decreasing drug efficacy. They control the xenobiotic detoxification system by regulating the exp...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.01.021
更新日期：2019-03-01 00:00:00
abstract：:Micro RNAs (miRNAs) are a class of naturally occurring ∼ 22 nt long non-coding small RNA molecules that regulate the expression of a wide range of genes involved in development, growth, proliferation and apoptosis. miRNAs are evolutionarily conserved from plants to animals, and they regulate and fine-tune a diverse ar...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2010.07.003
更新日期：2010-09-01 00:00:00
