Abstract：
PURPOSE:Short linear peptides have a high potential for delivering various drugs with therapeutic potential, including nucleic acids. Recently, we have shown that the cationic amphipathic histidine-rich peptide LAH4 (KKALLALALHHLAHLALHLALALKKA) possesses high plasmid DNA delivery capacities. Since such peptides are thought to efficiently disrupt endosomal membranes, we have tested their ability to deliver small interfering RNA (siRNA) into mammalian cells. METHODS:Using a human cell line stably transfected with a luciferase-encoding expression vector, we have evaluated the ability of LAH4 and five derivatives thereof to deliver siRNAs and silence gene expression. RESULTS:The six peptides are all efficient siRNA delivery vehicles whose efficiency in mediating gene silencing in 911-Luc cells was greater than that of commercially available compounds including Lipofectamine, DOTAP and polyethylenimine. In addition, by using the proton pump inhibitor bafilomycin A1, we show that efficient siRNA delivery to the cytosol requires acidification of the endosomes. CONCLUSIONS:The LAH4 histidine-rich cationic amphipathic peptides represent an interesting and promising family of compounds for siRNA delivery.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Langlet-Bertin B,Leborgne C,Scherman D,Bechinger B,Mason AJ,Kichler Adoi
10.1007/s11095-010-0138-2subject
Has Abstractpub_date
2010-07-01 00:00:00pages
1426-36issue
7eissn
0724-8741issn
1573-904Xjournal_volume
27pub_type
杂志文章abstract：PURPOSE:To investigate the effect of benzofusion on NO donor properties and related biological activities of the furoxan system. The biological properties considered were the ability to increase the cytosolic levels of cGMP in C6 cells and vasodilation. METHODS:NO donor properties were investigated either in the prese...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018974409622
更新日期：1999-06-01 00:00:00
abstract：PURPOSE:Nonlinear conjugation metabolic rate of valproic acid (VPA) has been speculated previously from plasma elimination and liver concentration of VPA in guinea pigs. The purposes of the present study were to assess our speculation by direct measurement of VPA glucuronidation rate in vitro. METHODS:VPA at various c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016028707130
更新日期：1996-08-01 00:00:00
abstract：:Over the last few decades, intraperitoneal (IP) local drug delivery, providing high drug concentrations with prolonged retention in the peritoneal cavity, has opened a new horizon for the management of life-threatening peritoneal disorders, such as peritoneal carcinomatosis (PC). However, clinical translation of this ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-020-02818-8
更新日期：2020-06-03 00:00:00
abstract：PURPOSE:The objective of this study was to elucidate the different mechanisms of action of different excipients on the oxidation of Met1, Met122, Met127, and Met138 in granulocyte colony-stimulating factor (G-CSF) by using hydrogen peroxide as the oxidant. METHODS:The oxidation of Met1, Met127, and Met138 was quantifi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-9019-x
更新日期：2005-01-01 00:00:00
abstract：:(+)-Propranolol was infused at two rates into the pyloric vein (a portal vein tributary) of 15 male Sprague Dawley rats until apparent steady-state conditions were established (i.e., 8 hr at each rate). One group (n = 7) received the high dose (40 micrograms/min/kg) first, and in the other group (n = 8) the low dose (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018921306200
更新日期：1994-03-01 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：PURPOSE:This work investigated the effect of relative humidity (RH) on bipolar electrostatic charge profiles of dry powder inhaler aerosols using the Bipolar Charge Analyzer (BOLAR). METHODS:Two commercial products, Pulmicort® (400 μg, budesonide) and Bricanyl® (500 μg, terbutaline sulfate) Turbuhaler®, were used as m...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2178-3
更新日期：2017-08-01 00:00:00
abstract：:The role of phosphatidylserine in the cellular and subcellular lung distribution of quinidine was investigated in rats, since quinidine was found to bind preferentially to phosphatidylserine. The concentration of phosphatidylserine in the cellular and subcellular fractions was determined after separation by two-dimens...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015985511653
更新日期：1988-04-01 00:00:00
abstract：PURPOSE:Hydrogen/deuterium (H/D) exchange over a range of temperatures suggests a protein structural/mobility transition in the solid state below the system glass transition temperature (Tg). The purpose of this study was to determine whether solid-state protein stability correlates with the difference between storage ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02897-7
更新日期：2020-08-13 00:00:00
abstract：PURPOSE:Effects of polyvinylpyrrolidone (PVP) molecular weight on the solid-state intermolecular interactions among probucol/PVP/sodium dodecyl sulfate (SDS) ternary ground mixtures (GM) and the formation of nanoparticles were investigated by solid-state NMR spectroscopy. MATERIALS AND METHODS:Ternary GMs of probucol ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9089-z
更新日期：2006-11-01 00:00:00
abstract：:Primaquine, an 8-aminoquinoline antimalarial, is shown to undergo unexpectedly rapid aromatic proton exchange with the medium. At a pH less than 4, the exchange of C-5 is so fast as to be unmeasurable by proton nmr methods. At a pH of 6-6.5 the half-time for exchange is 4 to 5 minutes. This unexpectedly high rate of e...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016356926714
更新日期：1984-07-01 00:00:00
abstract：PURPOSE:The aim of this study is to extend our previous studies to investigate the TerplexDNA synthetic gene carrier system in pharmacokinetics, biodistribution, and gene expression in major organs after systemic administration. METHODS:The stability of the TerplexDNA system was analyzed in vitro with a serum incubati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013081710135
更新日期：2001-09-01 00:00:00
abstract：PURPOSE:To evaluate different dissolution testing methods and subsequently develop a simple to perform but reproducible and discriminating dissolution technique for inhalative powders. METHODS:From a dry powder a fraction of aerosolized particles with an aerodynamic particle size below 5 μm was collected on regenerate...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0744-2
更新日期：2012-08-01 00:00:00
abstract：:The hair follicle, hair shaft, and sebaceous gland collectively form what is recognized as the pilosebaceous unit. This complex, three-dimensional structure within the skin possesses a unique biochemistry, metabolism and immunology. Recent studies have focused on the hair follicle as a potential pathway for both local...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1016250422596
更新日期：1995-02-01 00:00:00
abstract：PURPOSE:The purpose of this study was to clarify the localization and function of the ATP-binding cassette transporter G2 (ABCG2; BCRP/MXR/ABCP) in retinal capillary endothelial cells, which form the inner blood-retinal barrier, as an efflux transport system. METHODS:The expression was determined by reverse transcript...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-0067-2
更新日期：2006-06-01 00:00:00
abstract：PURPOSE:The aim was to replace the traditional 21-day Caco-2 permeability protocol by a more high-throughput assay. METHODS:Caco-2 cells were seeded at high density in 96-well plates in novel cell culture boxes. After 7 days, drug permeability studies were performed. Samples were analyzed by a new UV detection method....
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000008043.71001.43
更新日期：2003-12-01 00:00:00
abstract：PURPOSE:Pluronics are known as inhibitors of multidrug resistance thus making tumor cells sensitive to therapeutic doses of drugs. The purpose of our study consists in revealing molecular targets of the hydrophobic poly(propylene oxide) block of pluronics in living cells and the dependence of the polymers chemosensitiz...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2484-4
更新日期：2018-09-06 00:00:00
abstract：BACKGROUND:With the recent approval of the first small interfering RNA (siRNA) therapeutic formulated as nanoparticles, there is increased incentive for establishing the factors of importance for the design of stable solid dosage forms of such complex nanomedicines. METHODS:The aims of this study were: (i) to identify...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2663-y
更新日期：2019-08-02 00:00:00
abstract：PURPOSE:Polyesters with hydrophilic domains, i.e., poly(D,L-lactic-co-glycolic-co-hydroxymethyl glycolic acid) (PLGHMGA) and a multiblock copolymer of poly(ε-caprolactone)-PEG-poly(ε-caprolactone) and poly(L-lactide) ((PC-PEG-PC)-(PL)) are expected to cause less acylation of encapsulated peptides than fully hydrophobic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1685-3
更新日期：2015-09-01 00:00:00
abstract：BACKGROUND:Little is known about the affinity and stability of 99mTc-labeled 2-methoxyisobutylisonitrile (99mTc-MIBI) and tetrofosmin (99mTc-TF) for imaging of multiple drug resistance transporters in cancer. We examined the affinity of 99mTc-labeled compounds for these transporters and their stability. METHODS:99mTc-...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2548-5
更新日期：2018-11-29 00:00:00
abstract：PURPOSE:The study was performed for clarifying the mechanism of interaction between indoxyl sulfate (IS), a typical uremic toxin bound to site II, and site I-ligands when bound to human serum albumin (HSA). The effect of the N to B transition on the interactions was also examined. METHODS:Quantitative investigation of...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011014629551
更新日期：2001-04-01 00:00:00
abstract：PURPOSE:A mechanism-based PK-PD model was developed to predict the time course of dopamine D(2) receptor occupancy (D(2)RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. METHODS:A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of ol...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0477-7
更新日期：2011-10-01 00:00:00
abstract：PURPOSE:To examine the transport characteristics of the multidrug resistance-associated protein (MRP) substrate fluorescein across the isolated rat small intestinal segments. METHODS:The transport of fluorescein was studied in side-by-side diffusion chambers under short-circuited conditions at physiological pH. RESUL...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000022410.89709.c3
更新日期：2004-04-01 00:00:00
abstract：:The in situ rat gut technique was used to study the effects of hypothermia on the intestinal absorption of a 1 mg/ml solution of sodium pentobarbital in 0.01 M phosphate buffer (pH 6.0). Male Sprague-Dawley rats weighing between 300 and 370 g were exposed to an atmosphere of helox (helium:oxygen, 80:20) at 0-4 degrees...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016416413780
更新日期：1987-06-01 00:00:00
abstract：PURPOSE:Since the adoption of highly active antiretroviral therapy, HIV disease progression has slowed across the world; however, patients are often required to take multiple medications daily of poorly bioavailable drugs via the oral route, leading to gastrointestinal irritation. Recently, long acting antiretroviral i...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1936-y
更新日期：2016-08-01 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：PURPOSE:This study was aimed at developing a new active loading method to stably encapsulate staurosporine (STS), a water insoluble drug, into lipid-based nanoparticles (LNPs) for drug targeting to tumors. METHODS:A limited amount of DMSO was included during the active loading process to prevent precipitation and faci...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1854-4
更新日期：2016-05-01 00:00:00
abstract：PURPOSE:To examine the theoretical/practical utility of the liver-to-blood partition coefficient (Kpuu) for predicting drug-drug interactions (DDIs), and compare the Kpuu-approach to the extended clearance concept AUCR-approach. METHODS:The Kpuu relationship was derived from first principles. Theoretical simulations i...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02797-w
更新日期：2020-03-25 00:00:00
abstract：PURPOSE:Delivery of therapeutics to neurons is paramount to treat neurological conditions, including many lysosomal storage disorders. However, key aspects of drug-carrier behavior in neurons are relatively unknown: the occurrence of non-canonical endocytic pathways (present in other cells); whether carriers that trave...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1531-z
更新日期：2015-04-01 00:00:00
abstract：PURPOSE:The addition of high amounts of calcium remains a pharmaceutical concern due to its precipitation with phosphate in total parenteral nutrient (TPN) admixtures, compromising also the stability of the lipid emulsion. MATERIALS AND METHODS:Calcium-phosphate solubility was compared when using binary PN solutions v...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9671-7
更新日期：2008-11-01 00:00:00
