Abstract:
:Cellular uptake of therapeutic oligonucleotides and subsequent intracellular trafficking to their target sites represents the major technical hurdle for the biological effectiveness of these potential drugs. Accordingly, laboratories worldwide focus on the development of suitable delivery systems. Among the different available non-viral systems like cationic polymers, cationic liposomes and polymeric nanoparticles, cell-penetrating peptides (CPPs) represent an attractive concept to bypass the problem of poor membrane permeability of these charged macromolecules. While uptake per se in most cases does not represent the main obstacle of nucleic acid delivery in vitro, it becomes increasingly apparent that intracellular trafficking is the bottleneck. As a consequence, in order to optimize a given delivery system, a side-by-side analysis of nucleic acid cargo internalized and the corresponding biological effect is required to determine the overall efficacy. In this review, we will concentrate on peptide-mediated delivery of siRNAs and steric block oligonucleotides and discuss different methods for quantitative assessment of the amount of cargo taken up and how to correlate those numbers with biological effects by applying easy to handle reporter systems. To illustrate current limitations of non-viral nucleic acid delivery systems, we present own data as an example and discuss options of how to enhance trafficking of molecules entrapped in cellular compartments.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Laufer SD,Restle Tdoi
10.2174/138161208786898806subject
Has Abstractpub_date
2008-01-01 00:00:00pages
3637-55issue
34eissn
1381-6128issn
1873-4286journal_volume
14pub_type
杂志文章,评审abstract:BACKGROUND:Cancer is the world's second-largest cause of death, with an estimated 9.6 million fatalities in 2018. Malignant tumour (cancer) is caused by a mixture of genetic modifications due to the environmental variables that tend to activate or inactivate different genes, ultimately resulting in neoplastic transform...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200701151403
更新日期:2020-01-01 00:00:00
abstract::Pro-rich antimicrobial peptides are a group of linear peptides of innate immunity isolated from mammals and invertebrates, and characterised by a high content of proline residues (up to 50%). Members of this group are predominantly active against Gram-negative bacterial species which they kill by a non-lytic mechanism...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023395394
更新日期:2002-01-01 00:00:00
abstract::DNA-topoisomerases, a family of DNA-processing enzymes, represent the pharmacological target of major clinically useful chemotherapeutic agents. These drugs essentially act by trapping a topoisomerase-DNA cleavable complex, an intermediate in the enzyme s catalytic cycle. Research activity in this field continues to g...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1999-03-01 00:00:00
abstract::Hyperglycemia is a common feature of the critically ill in general and of patients with sepsis in particular. Even a moderate degree of hyperglycemia appears detrimental for the outcome of critically ill patients, since maintenance of normoglycemia (blood glucose levels journal_title:Current pharmaceutical design pub_type: 杂志文章,评审 doi:10.2174/138161208784980563 更新日期:2008-01-01 00:00:00
abstract::The solid lipid nanoparticles (SLNs) usually consists of active drug molecules along with solid lipids, surfactants, and/or co-surfactants. They possess some potential features such as nano-size, surface with a free functional group to attach ligands, and as well they prove safe homing for both lipophilic as well as h...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190903155321
更新日期:2019-01-01 00:00:00
abstract::ATP-sensitive K+ channels, termed K(ATP) channels, provide a link between cellular metabolism and membrane electrical activity in a variety of tissues. Channel isoforms have been identified and are targets for compounds that both stimulate and inhibit their activity resulting in membrane hyperpolarization and depolari...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054546879
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Clinic resting heart rate (RHR), is one of the cardiovascular parameters more easily measurable. In the general population RHR has been associated with total and cardiovascular mortality and higher rate of vascular events. OBJECTIVE:The case of essential hypertension is in some ways peculiar: in the past de...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170911102711
更新日期:2017-01-01 00:00:00
abstract::Stroke remains a major cause of death in the US and around the world. Despite major scientific advances in our understanding of stroke pathology, the only FDA-approved drug for ischemic stroke is tissue plasminogen activator (tPA). Moreover, the therapeutic window for tPA is confined to the acute phase of stroke, ther...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802002724
更新日期:2012-01-01 00:00:00
abstract::Adenosine is released in large amounts during myocardial ischemia and is capable of exerting potent cardioprotective effects in the heart. Although these observations on adenosine have been known for a long time, how adenosine acts to achieve its anti-ischemic effect remains incompletely understood. However, recent ad...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1999-12-01 00:00:00
abstract::The role of polyphenols in the cardiovascular diseases prevention is still a matter of scientific discussion. However, recent clinical studies indicate that intake of anthocyanins and in a lesser extent procyanidins can participate in prevention of hypertension and type 2 diabetes. Fruits of Aronia melanocarpa (chokeb...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151112152143
更新日期:2016-01-01 00:00:00
abstract::Recent advances in DNA sequencing has made it possible to accurately decipher the entire genetic complement of a probiotic bacterium. Increases in sequencing capabilities have been enhanced through improved computer software that can annotate, or identify, the majority of genes encoded by the sequence. The availabilit...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612053382377
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Atherosclerosis is a chronic inflammatory disease and a leading cause of coronary artery disease, peripheral vascular disease and stroke. Lipid-laden macrophages are derived from circulating monocytes and form fatty streaks as the first step of atherogenesis. METHODS:An electronic search in major databases ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190830153056
更新日期:2019-01-01 00:00:00
abstract::Development of effective drug delivery systems is important for medicine and healthcare. Polymer particulates (micro- and nanoparticles) have opened new opportunities in the field of drug delivery by overcoming various limitations of conventional delivery methods. The properties of polymeric particles can be readily t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160217125734
更新日期:2016-01-01 00:00:00
abstract::Metabolic syndrome is an aggregation of conditions and associated with an increased risk of developing diabetes, obesity and cardiovascular diseases (CVD). Edible mushrooms are widely consumed in many countries and are valuable components of the diet because of their attractive taste, aroma, and nutritional value. Med...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200831151316
更新日期:2020-01-01 00:00:00
abstract::Recent advances in the fabrication, characterization and application of micro- and nano-particles that possess a non-uniform internal structure are reviewed. The particle structures include core-shell particles, particles with multiple cores or a multi-layered structure, porous particles with both regular and random p...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319350007
更新日期:2013-01-01 00:00:00
abstract::The prevalence of obesity is increasing globally. Rational perioperative anesthetic drug selection and administration require knowledge of how obesity interacts with those drugs. In this review, we summarize different aspects of the anesthetic agents, including pharmacokinetics (PK), pharmacodynamics (PD) and clinical...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190628161206
更新日期:2019-01-01 00:00:00
abstract::This manuscript provides an overview for analysts, medical and scientific investigators, and laboratory administrators, the range of factors that should be considered to implement best practice forensic toxicology. These include laboratory influence over the collection of specimens, their proper transport and chain-of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170704123836
更新日期:2017-01-01 00:00:00
abstract::Molecular Mechanics (MM) force fields are the methods of choice for protein simulations, which are essential in the study of conformational flexibility. Given the importance of protein flexibility in drug binding, MM is involved in most if not all Computational Structure-Based Drug Discovery (CSBDD) projects. This pap...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990600
更新日期:2014-01-01 00:00:00
abstract::Fetal Alcohol Syndrome (FAS), the most severe manifestation of Fetal Alcohol Spectrum Disorder (FASD) is considered the leading non-hereditary cause of mental retardation and neurological deficit in the Western world. There lie a huge associated human cost to both FASD victims and their families and a considerable fin...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140205144114
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Approximately 10-15% of patients on DOACs have to interrupt their anticoagulant before an invasive procedure every year. The perioperative management and monitoring of DOACs have proved to be challenging, as differences in patients' status and in the invasiveness of each procedure develop different situation...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666181226154746
更新日期:2018-01-01 00:00:00
abstract::CD1 molecules are a family of non-polymorphic, class I antigen-presenting glycoproteins, which bind and present amphiphilic lipid antigens for recognition to T cells. Two groups of CD1 molecules are involved in presentation of self and foreign lipid antigens: group 1 (CD1a, CD1b and CD1c) and group 2 (CD1d). Crystal s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789105108
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Sulfur mustard (SM)-induced airway injuries and chronic obstructive pulmonary disease (COPD) are characterized by chronic inflammation of the respiratory tract and share some similarities regarding the cellular and molecular mechanisms orchestrating airway destruction. Since available data regarding the immu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160307150818
更新日期:2016-01-01 00:00:00
abstract::The search for methods to control physiological levels of carbon monoxide (CO), a vasoactive molecule, and bilibrubin, an antioxidant, have improved our understanding of the protective role of heme oxygenase (HO) against oxidative injury. HO activity can assist other antioxidant systems in diminishing the overall prod...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033453758
更新日期:2003-01-01 00:00:00
abstract::Providing novel treatments to help cancer patients live longer and have better lives remains one of the biggest challenges of the pharmaceutical industry. Today much is known about the molecular and genetic causes of cancers thus facilitating the development of novel targeted cancer drugs with improved risk-benefit ra...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784246234
更新日期:2008-01-01 00:00:00
abstract::Diet has a high relevance in health. Hypertension is a major risk factor for cardiovascular diseases and has an important impact on public health, and consequently on countries economy. Scientific research gathered strong evidence about the role of several dietary factors either in etiology or in treatment/prevention ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802651670
更新日期:2012-01-01 00:00:00
abstract::Monocytes are leading component of the mononuclear phagocytic system that play a key role in phagocytosis and removal of several kinds of microbes from the body. Monocytes are bone marrow precursor cells that stay in the blood for a few days and migrate towards tissues where they differentiate into macrophages. Monocy...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190102104642
更新日期:2018-01-01 00:00:00
abstract::Gene delivery, a process of introducing foreign functional nucleic acids into target cells, has proven to be a very promising tool for inducing specific gene expression in host cells. Many different technologies have been developed for efficient gene delivery. Among them, electroporation has been adopted in gene deliv...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666151027152121
更新日期:2015-01-01 00:00:00
abstract::Opiates lack potent analgesic efficacy in neuropathic pain although it is now generally accepted that the poor effect of these drugs reflects a reduction in their potency. Reduction of morphine antinociceptive potency was postulated to be due to the fact that nerve injury altered the activity of opioid systems or opio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054865055
更新日期:2005-01-01 00:00:00
abstract::A review of the Electron-Conformational (EC) method of pharmacophore (Pha) identification and quantitative bioactivity prediction in drug design and toxicology is presented, which includes the latest advances and improvements of the method as a whole and details of its realization with illustration of results. In the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454586
更新日期:2003-01-01 00:00:00
abstract::Antimicrobial photodynamic therapy (aPDT) is an emerging alternative to antibiotics motivated by growing problems with multi-drug resistant pathogens. aPDT uses non-toxic dyes or photosensitizers (PS) in combination with harmless visible of the correct wavelength to be absorbed by the PS. The excited state PS can form...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211795703735
更新日期:2011-01-01 00:00:00