Abstract：
PURPOSE:Following extracellular drug clearance, we analyzed the rate of doxorubicin efflux from the nucleus of three human leukemic cells (K562, Molt4 and CCRF-CEM) and related it to their differential sensitivity to this drug, after a short drug pulse. RESULTS:For many pulse-chase regimes, K562 cell viability was least affected by doxorubicin. In K562 cells, nuclear drug accumulation was greatest, but nuclear drug egress was also greatest. P-glycoprotein over-expression in a doxorubicin-resistant, K562/DOX sub-line did not facilitate doxorubicin efflux from the nucleus. In K562 cells, doxorubicin accumulated in multivesicular bodies (MVBs) through a pH-dependent mechanism. Inhibiting drug sequestration in MVBs did not affect nuclear efflux. The rates of doxorubicin efflux from the nuclei of live and digitonin-permeabilized K562 cells were similar. However, extracting cytoplasmic membranes with Triton X-100 significantly inhibited nuclear drug efflux following extracellular drug clearance. CONCLUSION:Our results are consistent with drug efflux from the nucleus being primarily mediated by an ATP-independent, passive diffusion mechanism. The effect of membrane extraction suggests that nonspecific drug absorption to cytoplasmic membranes plays a role in facilitating nuclear efflux in K562 cells, perhaps by lowering the concentration of free doxorubicin from a perinuclear diffusion boundary layer.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Chen VY,Posada MM,Zhao L,Rosania GRdoi
10.1007/s11095-007-9369-2subject
Has Abstractpub_date
2007-11-01 00:00:00pages
2156-67issue
11eissn
0724-8741issn
1573-904Xjournal_volume
24pub_type
杂志文章abstract：PURPOSE:To elucidate the catalytic mechanism of the esterase-like activity of serum albumin (SA), the reactivity of SA from six species was investigated using p-nitrophenyl esters as model substrates. METHODS:The effect of pH and the energetic and thermodynamic profiles of SA were determined for all species for p-nitr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000016241.84630.06
更新日期：2004-02-01 00:00:00
abstract：PURPOSE:To produce and characterize a nonviral ultrasound-controlled release system of plasmid DNA (pDNA) encapsulated in gas-filled poly(D,L-lactide-co-glycolide) microparticles (PLGA-MPs). METHODS:Different cationic polymers were used to form pDNA/polymer complexes to enhance the stability of pDNA during micropartic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1014430631844
更新日期：2002-03-01 00:00:00
abstract：PURPOSE:The aim was to evaluate fluorescent molecular rotors (DCVJ and CCVJ), which are mainly sensitive to viscosity, for the characterization of polysorbate-containing IgG formulations and compare them to the polarity-sensitive dyes ANS, Bis-ANS and Nile Red. METHODS:IgG formulations with polysorbate 20 or 80 were s...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-0020-2
更新日期：2010-02-01 00:00:00
abstract：PURPOSE:The aim of the study was to investigate whether dopamine is transferred along the olfactory pathway to the brain following nasal administration to mice. METHODS:[3H]-Dopamine was administered nasally or intravenously to female mice. Brain tissue samples were excised and the radioactive content was measured. Th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007542618378
更新日期：2000-06-01 00:00:00
abstract：:A procedure is described that is suitable for the radioimmunoassay (RIA) of 9-[(l,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) in plasma or serum at concentrations as low as 0.7 ng/ml (2.75 × 10(-9) M). Antiserum was prepared by coupling DHPG monohemisuccinate to bovine serum albumin and immunizing rabbits with the re...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016397520991
更新日期：1986-04-01 00:00:00
abstract：PURPOSE:Design of intravaginal rings (IVRs) for delivery of antiretrovirals is often guided by in vitro release under sink conditions, based on the assumption that in vivo release will follow a similar release profile. METHODS:We conducted a dose-ranging study in the female reproductive tract of pigtail macaques using...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2224-1
更新日期：2017-10-01 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：:Esmolol hydrochloride degrades in aqueous solutions by the hydrolysis of a labile aliphatic carboxyester group. The products are methanol and ASL-8123. The resulting aliphatic carboxylic acid moiety (ASL-8123) has a pK of 4.80, which is within 1 pH unit of the pH of the formulation. ASL-8123 therefore acts as a "secon...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015973425708
更新日期：1988-08-01 00:00:00
abstract：PURPOSE:Grapefruit juice (GJ) is known to increase the oral bioavailability of many CYP3A-substrates by inhibiting intestinal phase-I metabolism. However, the magnitude of AUC increase is often insignificant and highly variable. Since we earlier suggested that CYP3A and P-glycoprotein (P-gp) form a concerted barrier to...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011902625609
更新日期：1999-04-01 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:The purpose of the study was to examine the suitability of using laser diffraction to measure the fine particle fraction (FPF) of drugs emitted from carrier-free dry powder aerosol formulations. MATERIALS AND METHODS:Particle size distribution of terbutaline sulphate from Bricanyl Turbohaler, which contained l...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9056-8
更新日期：2006-09-01 00:00:00
abstract：PURPOSE:The effects of liposomes on nitric oxide (NO) production from mouse peritoneal macrophages following intraperitoneal injection of liposomes were investigated. METHODS:Mouse peritoneal macrophages were collected following intraperitoneal injection of liposomes and cultured with and without lipopolysaccharide (L...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016034303012
更新日期：1996-09-01 00:00:00
abstract：PURPOSE:To determine the different conformations of the acyloxyalkoxy-linked cyclic prodrug 1 of the model hexapeptide 2 in solution and to investigate the relationship between these solution conformations and the cellular permeability characteristics of this prodrug. METHODS:Two-dimensional Homonuclear Hartmann-Hahn ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016484522113
更新日期：1996-11-01 00:00:00
abstract：OBJECTIVE:Amorphous pharmaceuticals, a viable approach to enhancing bioavailability, must be stable against crystallization. An amorphous drug can be stabilized by dispersing it in a polymer matrix. To implement this approach, it is desirable to know the drug's solubility in the chosen polymer, which defines the maxima...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9784-z
更新日期：2009-04-01 00:00:00
abstract：PURPOSE:The pharmacokinetics of corticosteroids in pregnancy were analyzed to assess maternal/fetal disposition and factors controlling fetal exposure. Area/Moment equations and compartmental models for estimating pharmacokinetic parameters from single dose data during pregnancy were developed. METHODS:Betamethasone i...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-7681-7
更新日期：2004-12-01 00:00:00
abstract：PURPOSE:To co-crystallise mannitol and lactose with a view to obtaining crystals with more favourable morphological features than either lactose or mannitol alone, suitable for use as carriers in formulations for dry powder inhalers (DPIs) using simultaneous engineering of lactose-mannitol mixtures. METHODS:Mannitol a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0743-3
更新日期：2012-08-01 00:00:00
abstract：PURPOSE:Scutellarin, a flavonoid derived from the plant Erigeron breviscapus, is currently widely used to treat cerebrovascular diseases, liver-related diseases, and hyperlipidemia in china and other East Asian countries. This study was to investigate the effect of scutellarin on the uptake of rosuvastatin in HEK293T c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02950-5
更新日期：2020-10-29 00:00:00
abstract：PURPOSE:A theoretical study was performed to generate a pharmacophore model for chemically diverse structures that specifically interact with the diltiazem binding site of L-type calcium channels. METHODS:Via molecular mechanics and quantum chemical methods solvation energies, logP values, conformational and electroni...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015037800903
更新日期：1999-10-01 00:00:00
abstract：:Inkjet printing is an attractive material deposition and patterning technology that has received significant attention in the recent years. It has been exploited for novel applications including high throughput screening, pharmaceutical formulations, medical devices and implants. Moreover, inkjet printing has been imp...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-016-1931-3
更新日期：2016-08-01 00:00:00
abstract：PURPOSE:Generalizations based upon behavior of small molecules have established that a crystalline solid is generally much more stable toward chemical degradation than is the amorphous solid. This study examines the validity of this generalization for proteins using biosynthetic human insulin as the model protein. MET...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012164520429
更新日期：1997-10-01 00:00:00
abstract：PURPOSE:A thermodynamic analysis of the binding to rat cortex adenosine A1 receptor of N6-substituted (full agonists) and N6-substituted-deoxyribose (partial agonists) adenosine derivatives was performed. The intrinsic activity of the compounds was evaluated by measurements of the inhibition of forskolin stimulated 3',...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018987816891
更新日期：1999-07-01 00:00:00
abstract：PURPOSE:To investigate the possible pathways for transport of wheat germ agglutinin conjugated PEG-PLA nanoparticles (WGA-NP) into the brain after nasal administration. METHODS:The nose-to-brain pathways were investigated using WGA-NP containing 6-coumarin (as a fluorescent marker) and (125)I-labeled WGA-NP. Ex vivo i...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0641-0
更新日期：2012-02-01 00:00:00
abstract：PURPOSE:Reverse iontophoresis is an alternative to blood sampling for the monitoring of endogenous molecules. Here, the potential of the technique to measure urea and potassium levels non-invasively, and to track their concentrations during hemodialysis, has been examined. MATERIALS AND METHODS:In vitro experiments we...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9237-0
更新日期：2007-06-01 00:00:00
abstract：PURPOSE:In vitro in vivo correlation (IVIVC) is a biopharmaceutical tool recommended for use in formulation development. When validated, IVIVC can be used to set dissolution limits and, based on the dissolution limits, as a surrogate for an in vivo study. The purpose of this paper is to study the various methods used t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1349-8
更新日期：2014-09-01 00:00:00
abstract：:Sodium taurodihydrofusidate (STDHF) is one of the most promising absorption enhancers for nasal delivery of peptide drugs. Drugs and additives in nasal formulations should not interfere with the self-cleaning capacity of the nose by the ciliary epithelium. Measured in vitro on human adenoid tissue with a photoelectric...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015872617511
更新日期：1990-02-01 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 explore whether miR-19 is involved in the regulation of multidrug resistance (MDR), one of the main causes of breast cancer mortality, and modulates sensitivity of tumor cells to chemotherapeutic agents. METHODS:We analyzed miRNA expression levels in three MDR cell lines in comparison with their parent cell...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0570-y
更新日期：2011-12-01 00:00:00
abstract：:The pharmacokinetics of cefixime, a new orally active cephalosporin, was studied after an intravenous dose of 50 mg/kg to four beagle dogs. Cefixime was shown to exhibit concentration dependent serum protein binding and saturable tubular reabsorption. The drug was excreted mainly in the urine, the net result of glomer...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016309923717
更新日期：1986-06-01 00:00:00
abstract：:The area function method for assessing zero-order (ko) drug absorption rates was compared to four other methods under conditions where variation occurs in the plasma concentration data and in the elimination rate constant (kel or k10) for one- or two-compartment models. For deviant kel values of a one-compartment mode...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015843811150
更新日期：1990-01-01 00:00:00
abstract：PURPOSE:To compare the ability of alkyl-aryl isothiocyanates (ITCs) to increase the activities of the Phase 2 detoxification enzymes NAD[P]H:quinone acceptor oxidoreductase 1 (NQO1) and glutathione S-transferases (GST) in rat tissues in vivo and in cells in vitro. MATERIALS AND METHODS:Twelve alkyl-aryl ITCs and the f...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9595-2
更新日期：2008-09-01 00:00:00
