Abstract:
:RNA interference (RNAi) strategies include double-stranded RNA (dsRNA), small interfering RNA (siRNA), short hairpin RNA (shRNA), and microRNA (miRNA). As this is a highly specific technique, efforts have been made to utilize RNAi towards potential knock down of disease-causing genes in a targeted fashion. RNAi has the potential to selectively inhibit gene expression by degrading or blocking the translation of the target mRNA. However, delivering these RNAs to specific cells presents a significant challenge. Some of these challenges result from the necessity of traversing the circulatory system while avoiding kidney filtration, degradation by endonucleases, aggregation with serum proteins, and uptake by phagocytes. Further, non-specific delivery may result in side-effects, including the activation of immune response. We discuss the challenges in the systemic delivery to target cells, cellular uptake, endosomal release and intracellular transport of RNAi drugs and recent progress in overcoming these barriers. We also discuss approaches that increase the specificity and metabolic stability and reduce the off-target effects of RNAi strategy.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Singh S,Narang AS,Mahato RIdoi
10.1007/s11095-011-0608-1subject
Has Abstractpub_date
2011-12-01 00:00:00pages
2996-3015issue
12eissn
0724-8741issn
1573-904Xjournal_volume
28pub_type
杂志文章,评审abstract:PURPOSE:Indomethacin is well known to be metabolized via O-demethylation and N-deacylation. In this paper we found an enzyme involved in the hydrolysis of amide-linkage of indomethacin and partially characterized it as well as its substrate specificity. METHODS:An indomethacin hydrolyzing enzyme was purified to homoge...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016061614399
更新日期:1996-09-01 00:00:00
abstract::Lidocaine was administered to healthy volunteers at different sites in the rectum. Unchanged drug and monoethylglycinexylidide (MEGX) concentrations were measured in plasma with a newly developed gas chromatographic method. Lidocaine was given rectally by means of an osmotic system (Osmet(®)) which delivered 25 mg/h a...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016380104424
更新日期:1984-05-01 00:00:00
abstract::An oral formulation of controlled-release isosorbide-5-nitrate pellets has been used to investigate the location of pellets in the gastrointestinal (GI) tract and, in parallel, to measure the drug absorption from these locations. Using the method of gamma scintigraphy the transit times and spreading of pellets in the ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016423404636
更新日期:1987-12-01 00:00:00
abstract:PURPOSE:An integrated ionic mobility-pore model for epidermal iontophoresis is developed from theoretical considerations using both the free volume and pore restriction forms of the model for a range of solute radii (rj) approaching the pore radii (rp) as well as approximation of the pore restriction form for rj/rp < 0...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011907201096
更新日期:1998-10-01 00:00:00
abstract::Biotherapeutics, including recombinant or plasma-derived human proteins and antibody-based molecules, have emerged as an important class of pharmaceuticals. Aggregation and immunogenicity are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregati...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0414-9
更新日期:2011-05-01 00:00:00
abstract::Pharmacokinetic-pharmacodynamic modeling algorithms, in general, rely on hysteresis minimization techniques that assume time-invariant pharmacodynamics (constant biophase concentration-effect relationships). When time-variant pharmacodynamics are observed, a specific model for tolerance or sensitization is required. H...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018940122382
更新日期:1994-12-01 00:00:00
abstract:PURPOSE:The purpose of the present study was to explore the involvement of indoxyl sulfate (IS) in nephrotoxicity and central nervous system (CNS) toxicity in cisplatin (CDDP)-treated rats. MATERIALS AND METHODS:Renal function was evaluated by serum creatinine and BUN levels. The IS levels in the serum, brain and kidn...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9183-2
更新日期:2007-04-01 00:00:00
abstract:PURPOSE:Due to protease inhibitor (PI) efflux transport by P-glycoprotein (P-gp), insufficient PI concentrations result in low ongoing HIV replication in the so-called virus sanctuaries (brain and testes). The aim of the present study was to evaluate indinavir-loaded nanocapsules (Ind-LNC) including Solutol HS15, an ex...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-7147-6
更新日期:2005-11-01 00:00:00
abstract:PURPOSE:The purpose of this study was to characterize the amorphous state of ursodeoxycholic acid (UDCA) samples by using isothermal microcalorimetry, X-ray diffraction, infrared (IR) spectroscopy and solid state carbon 13 nuclear magnetic resonance (13C-NMR) spectroscopy, and to demonstrate the application of the ther...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012114825513
更新日期:1997-06-01 00:00:00
abstract:PURPOSE:Propofol is a widely used anesthetic agent with highly desirable fast "on" and "off" effects. It is currently formulated as lipid emulsions, which are known to support microbial growth. In this study, a novel, lipid-free nanodispersion formulation of propofol was characterized. METHODS:The formulation was eval...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-004-1872-0
更新日期:2005-03-01 00:00:00
abstract:PURPOSE:To develop novel bioactive-chylomicrons to solve oral delivery obstacles of Berberine chloride and target the lymphatic system. METHODS:Berberine-loaded bioactive-chylomicrons were prepared and underwent full in vitro characterization. Intestinal permeability was appraised via both non-everted gut sac model an...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2307-z
更新日期:2018-01-05 00:00:00
abstract::Transport studies using intestinal brush-border membrane vesicles isolated from rats and rabbits have failed to demonstrate proton- or Na(+)-dependent carrier-mediated transport of thyrotropin-releasing hormone (TRH), despite a pharmacologically relevant oral bioavailability. To examine the hypothesis that reported le...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018947430018
更新日期:1993-05-01 00:00:00
abstract:PURPOSE:S-(4-Nitrobenzyl)-6-thioinosine (NBMPR) is routinely used at concentrations of 0.10 μM and 0.10 mM to specifically inhibit transport of nucleosides mediated by equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2), respectively. We recently showed that NBMPR (0.10 mM) might also inhibit placental active e...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-2782-5
更新日期:2020-02-21 00:00:00
abstract::Physicochemical effects caused by intestinal fluids on drugs in the gastrointestinal (GI) tract can be a contributing factor in food induced changes in bioavailability. To identify physicochemical properties of gemfibrozil that may be altered by endogenous and dietary lipids, in vitro studies were conducted in model s...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018967401000
更新日期:1994-12-01 00:00:00
abstract:PURPOSE:Near-infrared reflectance spectroscopy (NIRS) was used to evaluate and quantify the effect of compression force on the NIR spectra of tablets. METHODS:Flat, white tablets with no orientation (scoring, etc.) were manufactured on a Stokes Rotary Tablet Press. NIRS was used to predict tablet hardness on the follo...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012071904673
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:To investigate the effects of small aliphatic pendent groups conjugated through an acid-sensitive linker to the core of brushed block copolymer micelles on particle properties. METHODS:The brushed block copolymers were synthesized by conjugating five types of 2-alkanone (2-butanone, 2-hexanone, 2-octanone, 2-d...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1060-1
更新日期:2013-08-01 00:00:00
abstract:PURPOSE:To study the role of unsaturated fatty acid ester substituents in the autoxidation of polysorbate 80 using quantitative kinetics. METHODS:Oxidation kinetics were monitored at 40 degrees C in aqueous solution by tracking head space oxygen consumption using a fiber optic oxygen sensor with phase shift fluorescen...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-9946-7
更新日期:2009-10-01 00:00:00
abstract::Nasal sprays containing different concentrations of the somatostatin analogue octreotide and sodium tauro-24,25-dihydrofusidate (STDHF) as an absorption promoter were evaluated in two consecutive pharmacokinetic studies in healthy volunteers to characterize their bioavailability and local tolerability. The concentrati...
journal_title:Pharmaceutical research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1018927710280
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:Cannabinoids have been associated with tumor regression and apoptosis of cancer cells. Recently, we have shown that R(+)-methanandamide (R(+)-MA) induces apoptosis of H4 human neuroglioma cells via a mechanism involving de novo expression of the cyclooxygenase-2 (COX-2) enzyme. The present study investigated a ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-8815-2
更新日期:2006-01-01 00:00:00
abstract:PURPOSE:Bioavailability of orally administered drugs is much influenced by the behavior, performance and fate of the dosage form within the gastrointestinal (GI) tract. Therefore, MRI in vivo methods that allow for the simultaneous visualization of solid oral dosage forms and anatomical structures of the GI tract have ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012161630481
更新日期:1997-08-01 00:00:00
abstract:PURPOSE:This study aimed to develop a sustained-release formulation of exenatide (EXT) for the long-term therapeutic efficacy in the treatment of type II diabetes. METHODS:In this study, we present an injectable phospholipid gel by mixing biocompatible phospholipid S100, medium chain triglyceride (MCT) with 85% (w/w) ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-1873-9
更新日期:2016-06-01 00:00:00
abstract::The interaction of dicumarol and phenothiazine neuroleptics binding to alpha 1-acid glycoprotein (AGP) was investigated by circular dichroism (CD) and equilibrium dialysis. The induced CD spectra of the dicumarol-AGP complex were affected differently by the different substituents of the phenothiazine molecule. The sig...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015880327911
更新日期:1992-07-01 00:00:00
abstract::Since ancient times, natural products, herbs and spices have been used for preventing several diseases, including cancer. The term chemoprevention was coined in the late 1970s and referred to the prevention of cancer by selective use of phytochemicals or their analogs. The field utilizes experimental carcinogenesis mo...
journal_title:Pharmaceutical research
pub_type: 历史文章,杂志文章,评审
doi:10.1007/s11095-010-0085-y
更新日期:2010-06-01 00:00:00
abstract:PURPOSE:There is evidence that cholesterol affects the ATPase and transport functions of P-glycoprotein (P-gp). To study the influence of cholesterol on P-gp in a well defined lipid environment, we reconstituted P-gp in egg phosphatidylcholine (PhC) and PhC/cholesterol proteoliposomes with negligible residual amounts o...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9326-0
更新日期:2007-11-01 00:00:00
abstract:PURPOSE:To characterize factor(s) contained in apical medium of primary cultured rat alveolar epithelial type II cell-like monolayers (RAECM-II) that enhance insulin absorption across alveolar epithelial cells. MATERIALS AND METHODS:Primary rat alveolar epithelial cell monolayers cultured on Transwells in the presence...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9301-9
更新日期:2007-09-01 00:00:00
abstract::The effects of skin storage, skin preparation, skin pretreatment with a penetration enhancer, and skin barrier removal by adhesive tape-stripping on the concurrent cutaneous transport and metabolism of nitroglycerin (GTN) have been studied in vitro using hairless mouse skin. Storing the skin for 10 days at 4 degrees C...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015822431178
更新日期:1992-03-01 00:00:00
abstract::The dermal route is an attractive route for vaccine delivery due to the easy skin accessibility and a dense network of immune cells in the skin. The development of microneedles is crucial to take advantage of the skin immunization and simultaneously to overcome problems related to vaccination by conventional needles (...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-017-2223-2
更新日期:2017-11-01 00:00:00
abstract:PURPOSE:VLPs displaying tumor targeting single-chain variable fragments (VLP-rscFvs) which targets tumor-associated glycoprotein-72 (TAG-72) marker protein have a potential for immunotherapy against colon carcinoma tumors. In this study, scFvs anchored on VLPs using glycosylphosphatidylinositol (GPI) were prepared to t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1316-4
更新日期:2014-08-01 00:00:00
abstract:PURPOSE:In this study we aimed to evaluate adaptive designs (ADs) by clinical trial simulation for a pharmacokinetic-pharmacodynamic model in oncology and to compare them with one-stage designs, i.e., when no adaptation is performed, using wrong prior parameters. METHODS:We evaluated two one-stage designs, ξ0 and ξ*, ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1693-3
更新日期:2015-10-01 00:00:00
abstract:PURPOSE:Prostaglandin E(1) (PGE(1)) is an effective treatment for peripheral vascular diseases. The encapsulation of PGE(1) in nanoparticles for its sustained-release would improve its therapeutic effect and quality of life (QOL) of patients. METHODS:In order to encapsulate PGE(1) in nanoparticles prepared with a poly...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-9891-5
更新日期:2009-07-01 00:00:00