Abstract:
:Small interfering RNA (siRNA) that silence genes by the process of RNA interference offers a new therapeutic modality for disease treatment. Polycation-based nanoparticles termed polyplexes have been developed to maximise extracellular and intracellular siRNA delivery, a key requirement for enabling the clinical translation of RNAi-based drugs. Medical applications are dependent on safety; therefore, detailed investigation into potential toxicity to the cell or organism is required. This review addresses potential adverse effects arising from cellular and tissue interactions, immune stimulation and altered gene expression that can be associated with the assembled polyplex or the polycation and siRNA component parts. A greater understanding of the cellular mechanisms involved allows design-based solutions for rationale development of safe, effective and clinically relevant polyplex-based RNAi drugs.
journal_name
Adv Drug Deliv Revjournal_title
Advanced drug delivery reviewsauthors
Ballarín-González B,Howard KAdoi
10.1016/j.addr.2012.07.004subject
Has Abstractpub_date
2012-12-01 00:00:00pages
1717-29issue
15eissn
0169-409Xissn
1872-8294pii
S0169-409X(12)00223-2journal_volume
64pub_type
杂志文章,评审abstract::Mitochondria represent both the main source and target of reactive oxygen and nitrogen species (RONS). In view of the large energy expenditure made by neurons during neurotransmission, an intact mitochondrial function is of paramount importance for the correct function of the brain. Accordingly, the search of therapeu...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2009.05.009
更新日期:2009-11-30 00:00:00
abstract::The complexity of nanoscale interactions between biomaterials and cells has limited the realization of the ultimate vision of nanotechnology in diagnostics and therapeutics. As such, significant effort has been devoted to advancing our understanding of the biophysical interactions of the myriad nanoparticles. Endocyto...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2019.08.004
更新日期:2019-04-01 00:00:00
abstract::Nano- and microfabrication techniques have been widely explored in the textile, polymer and biomedical arenas, although more recently these systems have attracted considerable interest as drug delivery vehicles with concomitant considerations of physical characterization, scalability, stability and drug release. In th...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2016.01.003
更新日期:2016-05-01 00:00:00
abstract::Spray drying is a well-established manufacturing technique which can be used to formulate amorphous solid dispersions (ASDs) which is an effective strategy to deliver poorly water soluble drugs (PWSDs). However, the inherently complex nature of the spray drying process coupled with specific characteristics of ASDs mak...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2015.12.010
更新日期:2016-05-01 00:00:00
abstract::Genome-editing tools such as Cre recombinase (Cre), zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and most recently the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein system have revolutionized biomedical research, agriculture, microbial e...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2020.09.004
更新日期:2021-01-01 00:00:00
abstract::Toll-like receptor 9 (TLR9) agonists have demonstrated substantial potential as vaccine adjuvants, and as mono- or combination therapies for the treatment of cancer and infectious and allergic diseases. Commonly referred to as CpG oligodeoxynucleotides (ODN), TLR9 agonists directly induce the activation and maturation...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2008.12.008
更新日期:2009-03-28 00:00:00
abstract::Lanthanide-doped upconverting luminescent nanoparticles (UCNPs) are promising materials for optical imaging-guided drug delivery and therapy due to their unique optical and chemical properties. UCNPs absorb low energy near-infrared (NIR) light and emit high-energy shorter wavelength photons. Their special features all...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2012.05.007
更新日期:2013-05-01 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::New pharmaceutical formulations must be proven as safe and effective before entering clinical trials. Also in the context of pulmonary drug delivery, preclinical models allow testing of novel antimicrobials, reducing risks and costs during their development. Such models allow reducing the complexity of the human lung,...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2014.10.011
更新日期:2015-05-01 00:00:00
abstract::Drug resistance involves multiple mechanisms. Multidrug resistance (MDR) is the leading cause of treatment failure in cancer therapy. Elevated levels of MDR proteins [members of the ATP-binding cassette (ABC) transporter family] increase cellular efflux and decrease the effectiveness of chemotherapeutic agents. As a s...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2010.07.008
更新日期:2010-10-30 00:00:00
abstract::This article reviews the studies on skin electroporation carried out in vivo in animals and emphasizes its potential therapeutic applications for transdermal and topical drug delivery. In agreement with in vitro studies, transport across skin due to high-voltage pulses in vivo was shown to increase by orders of magnit...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(98)00064-7
更新日期:1999-01-04 00:00:00
abstract::Carbon-based functional nanomaterials have attracted immense scientific interest from many disciplines and, due to their extraordinary properties, have offered tremendous potential in a diverse range of applications. Among the different carbon nanomaterials, graphene is one of the newest and is considered the most imp...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2016.08.009
更新日期:2016-10-01 00:00:00
abstract::In this review we discuss mucus, the viscoelastic secretion from goblet or mucous producing cells that lines the epithelial surfaces of all organs exposed to the external world. Mucus is a complex aqueous fluid that owes its viscoelastic, lubricating and hydration properties to the glycoprotein mucin combined with ele...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2017.09.023
更新日期:2018-01-15 00:00:00
abstract::Microbubbles are used as ultrasonic contrast agents that enhance the ultrasound signals of the vascular bed. The recent development of site-targeted microbubbles opened up the possibility for molecular imaging as well as localised drug and gene delivery. Initially the microbubbles' physical properties and their respon...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2008.03.011
更新日期:2008-06-30 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::Amphiphilic polymers are particularly useful for drug delivery because of their ability to self-assemble into discrete aggregates. While this behavior has been studied in depth for simple linear block copolymer amphiphiles, recent advances in synthetic methodologies have provided efficient routes to amphiphilic polyme...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2012.03.011
更新日期:2012-06-15 00:00:00
abstract::Ruminants have a specialised digestive system that contains anaerobic bacteria and protozoa capable of digesting the cellulosic materials that are so common in plant materials. In addition, their distinct digestive system can change the metabolism and mode of action of some nutrients, medicines or other bioactive mate...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2004.02.011
更新日期:2004-06-23 00:00:00
abstract::The administration of radiolabeled compounds with gamma-emitting radionuclides allows real time pursuit of in vivo behavior of the compounds by external counting of the radioactivity. If the compounds possess a specific localization mechanism to target tissue, the image reflects the specific function of the target. Th...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(98)00102-1
更新日期:1999-04-05 00:00:00
abstract::The effective delivery of antigens via the oral route is an extremely desirable goal. Mucosal delivery of antigens stimulates mucosal and systemic immunity without affecting maternal antibodies and reduces the need for sterile needles or trained personnel. To date, there are very few commercially available oral vaccin...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2004.09.009
更新日期:2005-01-10 00:00:00
abstract::With inhalational delivery the alveolar epithelium appears to be the appropriate lung surface to target for the systemic delivery of macromolecules, such as therapeutic proteins. The existence of a high numerical density of smooth-coated or non-coated plasma membrane vesicles or invaginations within the alveolar epith...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(01)00142-9
更新日期:2001-07-28 00:00:00
abstract::Oral lipid-based drug delivery systems may include a broad range of oils, surfactants, and cosolvents. This diversity makes comparison of lipid-based formulations difficult. Although the relationship between formulation and drug absorption is understood at a conceptual level, performance in vivo cannot be predicted wi...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2007.10.010
更新日期:2008-03-17 00:00:00
abstract::In recent years, nanotechnology has offered attractive opportunities to overcome the (bio)pharmaceutical drawbacks of most drugs such as low aqueous solubility and bioavailability. Among the numerous methodologies that have been applied to improve drug performance, a special emphasis has been made on those that increa...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.07.012
更新日期:2018-06-01 00:00:00
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-relevan...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2013.12.005
更新日期:2014-04-01 00:00:00
abstract::Migraine is a debilitating disease that affects 9% of men and 19% of women worldwide with high socio-economic and personal impact. Surveys indicate that migraineurs are among the most dissatisfied with available therapeutic options, predominantly given via oral or injectable routes, citing side effects as the primary ...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.08.014
更新日期:2018-08-01 00:00:00
abstract::Cardiovascular functions such as heart rate and blood pressure show 24h variation. The incidence of cardiovascular diseases including acute myocardial infarction and arrhythmia also exhibits diurnal variation. The center of this circadian clock is located in the suprachiasmatic nucleus in the hypothalamus. However, re...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2010.04.011
更新日期:2010-07-31 00:00:00
abstract::Gene delivery to bone is useful both as an experimental tool and as a potential therapeutic strategy. Among its advantages over protein delivery are the potential for directed, sustained and regulated expression of authentically processed, nascent proteins. Although no clinical trials have been initiated, there is a s...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2012.03.013
更新日期:2012-09-01 00:00:00
abstract::Lack of approved pharmaceutical agents and/or pharmacokinetic data in the literature for exotic, wildlife, and zoo species is a major issue for veterinarians. These practitioners must take approved agents (veterinary or human) and extrapolate their use to non-approved species with little or no scientific basis to supp...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(02)00068-6
更新日期:2002-10-04 00:00:00
abstract::In the preparation of biomimetic materials it is often required that efficient methods of polymerization be used, often methods that can lead to biomimetic polymers with relatively narrow molecular weight distribution. Living radical polymerization techniques have successfully been used to create low polydispersity li...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2003.10.046
更新日期:2004-09-22 00:00:00
abstract::Many drug molecules possess inadequate physical-chemical characteristics that prevent to surpass the viscous mucus layer present in the surface of mucosal tissues. Due to mucus protective role and its fast turnover, these drug molecules end up being removed from the body before being absorbed and, thus, before exertin...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2017.09.020
更新日期:2018-01-15 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