Abstract:
PURPOSE:Previous studies by other investigators have shown an enhancement of mitomycin C (MMC) activity at acidic extracellular pH (pHe) in monolayer cultures of human cells. The goal of the present study was to determine if the efficacy of intravesical MMC therapy in patients treated for superficial bladder cancer can be enhanced by using acidified dosing solutions. We evaluated (a) the effect of pHe on MMC activity in patient bladder tumors in vitro, and (b) the pH dependency of MMC activity in 2-dimensional monolayer and 3-dimensional multilayer cultures of human bladder RT4 tumor cells. METHODS:Patient bladder tumors were maintained as 3-dimensional histocultures. RT4 cells were harvested and maintained as monolayer cultures or as 3-dimensional cell pellets on a collagen gel matrix. The cell pellets were 300-450 cell layers and 4,000-5,000 microns in diameter. Tumors or cells were incubated for 2 hr with MMC-containing media at pHe of 5, 6, and 7.4. The drug effect was measured by the inhibition of DNA precursor (thymidine) incorporation. The stability of MMC as a function of pHe was determined. About 24% of MMC was degraded following 2 hr exposure at pHe 5 and < or = 2% at pHe 6 and 7.4. RESULTS:The drug concentrations required to inhibit thymidine incorporation by 50% (IC50) were corrected for the degraded MMC at acidic pHe. The results showed no pH-dependent MMC activity in human patient bladder tumors nor in RT4 multilayer cultures; the IC50 values were about 10 micrograms/ml at all three pHe. In contrast, the monolayer RT4 cultures showed a pH-dependent MMC cytotoxicity; the IC50 were 0.1, 0.8 and 1.2 micrograms/ ml at pHe 5, 6 and 7.4, respectively (p < 0.05). Pre-incubation of multilayered RT4 cultures in acidic pH medium for 8 hr enhanced the MMC activity; the IC50 was reduced by about 5 fold at pHe about 3 fold at pHe 6. Similar pH-dependent MMC activity was found when multilayers were pre-treated for 1 hr with 0.5 microgram/ml nigericin, a proton ionophore known to cause the intracellular pH (pHi) to equilibrate with pHe. CONCLUSIONS:These data suggest that the difference in the pH dependency of MMC activity in the monolayer and multilayer systems was due to the different experimental conditions. The time lag for pHi to equilibrate with pHe in the multilayer systems and the instability of MMC at low pHe imply that the efficacy of intravesical MMC therapy is unlikely to be enhanced by using acidic dosing solution.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Yen WC,Schmittgen T,Au JLdoi
10.1023/a:1016053729362subject
Has Abstractpub_date
1996-12-01 00:00:00pages
1887-91issue
12eissn
0724-8741issn
1573-904Xjournal_volume
13pub_type
杂志文章abstract:PURPOSE:To investigate the effect of tyrphostin 8 (T-8), a GTPase inhibitor, on transferrin receptor (TfR)-mediated transcytosis of insulin-transferrin (In-Tf) conjugate in cultured enterocyte-like Caco-2 cells and on gastrointestinal (GI) absorption of In-Tf in streptozotocin (STZ)-induced diabetic rats. METHODS:Caco...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011032502097
更新日期:2001-02-01 00:00:00
abstract:PURPOSE:The aim of this work was to develop PEGylated poly(alkylcyanoacrylate) nanoparticles from a novel methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate copolymer. METHODS:PEGylated and non-PEGylated nanoparticles were formed by nanoprecipitation or by emulsion/solvent evaporation. Nanoparticles si...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011973625803
更新日期:1998-04-01 00:00:00
abstract:PURPOSE:To develop a new technique, spray freeze drying, for preparing protein aerosol powders. Also, to compare the spray freeze-dried powders with spray-dried powders in terms of physical properties and aerosol performance. METHODS:Protein powders were characterized using particle size analysis, thermogravimetric an...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018828425184
更新日期:1999-02-01 00:00:00
abstract:PURPOSE:The growing amount of heterogeneous bioactivity data requires effective strategies to assess the promiscuity/selectivity of small-molecules and aid drug discovery. In the current study, we aim to evaluate the potential of assay profiles (APs, i.e., unique combinations of assay-related features describing how ac...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2523-1
更新日期:2018-10-18 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::Interogan variation in tissue distribution of weakly basic drugs such as quinidine, propranolol, and imipramine was investigated as a function of binding to phosphatidylserine (PhS) in tissues. Tissue distributions of these drugs were determined using 10 different tissues at a steady-state plasma concentration and wer...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015935031933
更新日期:1990-10-01 00:00:00
abstract:PURPOSE:Our previous studies indicated that drug leaked from discoidal reconstituted high density lipoprotein (d-rHDL) during the remodeling behaviors induced by lecithin cholesterol acyl transferase (LCAT) abundant in circulation, thus decreasing the drug amount delivered into the target. In this study, arachidonic ac...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1273-3
更新日期:2014-07-01 00:00:00
abstract:PURPOSE:Recently identified organic solute transporter (Ost) alpha and beta are located on the basolateral membrane of enterocytes and may be responsible for the intestinal absorption of many substrates including bile acids. In the present study, the mechanism governing the transcriptional regulation of their expressio...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9163-6
更新日期:2007-02-01 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::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::During the past two decades the nanomedicine field has experienced significant progress. To date, over sixty nanoparticle (NP) formulations have been approved in the US and EU while many others are in clinical or preclinical development, indicating a concerted effort to translate promising bench research to commercial...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-019-2736-y
更新日期:2019-12-11 00:00:00
abstract:PURPOSE:Because interleukin-10 (IL-10) seems a promising new antifibrotic drug, we investigated the pharmacokinetic and biodistribution profile of this potent therapeutic cytokine in rats with extensive liver fibrosis (BDL-3). IL-10 receptor expression was also determined in relation to these aspects. METHODS:To study...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000048199.94510.b0
更新日期:2004-11-01 00:00:00
abstract:PURPOSE:We recently developed prostaglandin E(1) (PGE(1))-encapsulated nanoparticles, prepared with a poly(lactide) homopolymer (PLA, Mw = 17,500) and monomethoxy poly(ethyleneglycol)-PLA block copolymer (PEG-PLA) (NP-L20). In this study, we tested whether the accelerated blood clearance (ABC) phenomenon is observed wi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-9943-x
更新日期:2009-10-01 00:00:00
abstract:PURPOSE:To determine the pharmacokinetics of GS-522, an oligodeoxynucleotide (GGTTGGTGTGGTTGG) inhibitor of thrombin, after constant infusion and bolus administration in the cynomolgus monkey. METHODS:Using a stability indicating HPLC method, the GS-522 plasma concentration versus time data were obtained after constan...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016295907266
更新日期:1995-12-01 00:00:00
abstract:PURPOSE:The purpose of this investigation was to determine the influence on the antimicrobial activity of cetylpyridinium chloride of the various components of the formulation of each of six candy based lozenges. METHODS:In vivo activity was investigated using six volunteers by determining the reduction in colony form...
journal_title:Pharmaceutical research
pub_type: 临床试验,杂志文章
doi:10.1023/a:1016002322692
更新日期:1996-04-01 00:00:00
abstract:PURPOSE:The low aqueous solubility of many drugs impedes detailed investigation as the detection limit of standard testing routines is limited. This is further complicated within application relevant thin films typical used in patches or stripes for buccal or topical routes. METHODS:In this work a model system is deve...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1368-5
更新日期:2014-10-01 00:00:00
abstract:PURPOSE:The purpose of this study was to evaluate an effect of the proteolytic enzyme papain on permeation of low molecular weight heparin (LMWH) in vitro and in vivo. MATERIALS AND METHODS:In vitro permeation studies were performed using rat small intestine as permeation barrier. In order to determine the ratio of pa...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9226-8
更新日期:2007-05-01 00:00:00
abstract:PURPOSE:To develop resource-sparing in silico approaches that aim to reduce experimental effort and material required by developability assessments (DA) of monoclonal antibody (mAb) drug candidates. METHODS:A battery of standardized biophysical experiments was performed on high concentration formulations of 16 drug pr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2466-6
更新日期:2018-08-20 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::Photodegradation of solutions of metronidazole in the presence and absence of sodium urate was studied. Photodegradation appeared to follow zero-order kinetics and was found to be dependent on the pH, buffer species, sodium urate concentration, and light source. Complex formation between metronidazole and sodium urate...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015851719579
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:To develop a safe and effective non-viral vector for gene delivery and transfection in macrophages for potential anti-inflammatory therapy. METHODS:Solid nanoparticles-in-emulsion (NiE) multi-compartmental delivery system was designed using plasmid DNA-encapsulated type B gelatin nanoparticles suspended in the...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0677-9
更新日期:2012-06-01 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:E-selectin is a cell adhesion molecule that is specifically expressed in the inflammatory vascular endothelium in response to cytokines such as IL-1 beta and TNF-alpha, and interacts with specific ligands containing sialyl Lewis X (Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-, SLex). In order to investiga...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018849029727
更新日期:1999-02-01 00:00:00
abstract:PURPOSE:(i) To use trehalose as a model compound to evaluate the concept of crystallinity in pharmaceuticals. (ii) To understand the structural nature of dehydrated trehalose dihydrate. MATERIALS AND METHODS:Trehalose dihydrate was dehydrated isothermally at several temperatures below 100 degrees C and the anhydrous p...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9058-6
更新日期:2006-10-01 00:00:00
abstract:PURPOSE:To investigate how likely two extended release formulations are to be bioequivalent when they demonstrate f2 similarity. METHOD:Dissolution profiles were simulated using the Weibull model and varying model parameters around those of a reference profile. The f2 values were calculated for the comparisons of each...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0377-x
更新日期:2011-05-01 00:00:00
abstract:PURPOSE:Heparin immobilized porous poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared for sustained release of basic fibroblast growth factor (bFGF) to induce angiogenesis. MATERIALS AND METHODS:Porous PLGA microspheres having primary amine groups on the surface were prepared using an oil-in-water (O/...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9039-9
更新日期:2006-08-01 00:00:00
abstract:PURPOSE:Chitosan and its derivatives possess several unique properties relevant in the field of pharmaceutics and medicinal chemistry. This study aimed to evaluate the pharmaceutical performance of an innovative chitosan derivative, methyl acrylate chitosan bearing p-nitrobenzaldehyde (MA*CS*pNBA) Schiff base. METHODS...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2535-x
更新日期:2018-11-07 00:00:00
abstract::The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent wi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015834114359
更新日期:1991-12-01 00:00:00
abstract:PURPOSE:Pancreatic cancer remains the fourth most common cause of cancer-related death in the United States. Therefore, novel strategies for the prevention and/or treatment are urgently needed. Genistein has been found to be responsible for lowering the rate of pancreatic cancer. However, the molecular mechanisms by wh...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0106-x
更新日期:2010-06-01 00:00:00
abstract::Nanoparticles, including lipopolyamines leading to lipoplexes, liposomes, and polyplexes are targeted drug carrier systems in the current search for a successful delivery system for polynucleic acids. This review is focused on the impact of gene and siRNA delivery for studies of efficacy, pharmacodynamics, and pharmac...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-008-9646-8
更新日期:2009-01-01 00:00:00