Abstract：
:Cyclosporin A (CyA) interacts with lipid membranes. Binding reaction and membrane location of CyA and analogs were examined with 2H-NMR, high-sensitivity isothermal titration calorimetry (ITC), and CD spectroscopy. Effects of CyA and charged analogs on the phosphocholine head group and on the membrane interior were investigated using selectively deuterated phospholipids. Incorporation of cyclosporin generated small disordering of the lipid acyl chains. Binding of CyA and neutral and positively charged analogs to lipid membranes showed endothermic heats of reaction between + 5.9 and + 11.3 kcal/mol, whereas enthalpy of binding was close to zero for the negatively charged derivative. Binding constants of cyclosporines to liposomal membranes were in the range of K(P) = 1650-5560 M(- 1) depending on the cholesterol content. (2)H-NMR provides evidence that CyA is essentially located in the interior of the bilayer membrane. For the charged analogs an additional interaction occurs at the head group level, placing the polar groups of these CyA analogs in the vicinity of the phosphocholine dipoles. The association of CyA and its analogs is accompanied by a positive enthalpy change, which is overcompensated by positive entropy changes. Binding of CyA to lipid membranes thus follows the classical hydrophobic effect, which is in contrast to many other peptide-lipid binding reactions.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Schote U,Ganz P,Fahr A,Seelig Jdoi
10.1002/jps.10071subject
Has Abstractpub_date
2002-03-01 00:00:00pages
856-67issue
3eissn
0022-3549issn
1520-6017pii
S0022-3549(16)30942-Xjournal_volume
91pub_type
杂志文章abstract：:The aim of this study was to evaluate a new experimental protocol utilizing isolated frog intestinal sacs for the assessment of intestinal drug permeability in humans. Segments of approximately 5.0 cm in length were used for these experiments. The intestinal sacs were filled with a solution of the appropriate drug in ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20180
更新日期：2004-12-01 00:00:00
abstract：:Isoperibol calorimetry was used to evaluate protein/carbohydrate interactions after freeze drying. rh-DNase, rh-GH, rh-MetGH, and rh-IGF-I were freeze dried with either mannitol, sucrose, trehalose, or dextran at concentrations ranging from 0% to 100% (w/w). Enthalpies of solution for both freeze-dried and physical mi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10023
更新日期：2002-01-01 00:00:00
abstract：:Bacmecillinam is an amdinocillin prodrug designed to be easily hydrolyzed in biological materials, so special procedures were developed for the collection of blood specimens. Whole blood was collected in tubes containing bacampicillin as an adsorption inhibitor and kept at -70 degrees; the extracting solvent, hexane-m...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600711018
更新日期：1982-10-01 00:00:00
abstract：:The dissolution characteristics of dicumarol were markedly enhanced by preparing dispersions of drug in polyethylene glycol 4000. Solid dispersions of varying weight fractions were formed by a melt method without measurable drug degradation or evaporation. There were no significant differences in dissolution rates amo...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600701217
更新日期：1981-12-01 00:00:00
abstract：:Simulated intestinal media (SIM) containing bile salt (BS) and phospholipids (PL) with and without medium chain lipolytic products (MC-LP) or long chain lipolytic products (LC-LP) were developed to study the solubility of seocalcitol. Both MC-LP and LC-LP were studied in order to investigate the influence of fatty aci...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20403
更新日期：2005-08-01 00:00:00
abstract：:Metronidazole (MTZ) is a drug of choice for protozoal infections such as luminal amoebiasis. We designed and synthesized N-nicotinoyl-2-{2-(2-methyl-5-nitroimidazol-1-yl)ethyloxy}-D,L-glycine (NMG) as a colon-specific prodrug of MTZ. The synthetic yield of NMG was about 34%. The apparent partition coefficient of MTZ w...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21720
更新日期：2009-11-01 00:00:00
abstract：:The aim of the present study was to investigate the mechanism of aqueous degradation of Salinosporamide A (NPI-0052; 1), a potent proteasome inhibitor that is currently in Phase I clinical trials for the treatment of cancer and is characterized by a unique beta-lactone-gamma-lactam bicyclic ring structure. The degrada...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20835
更新日期：2007-08-01 00:00:00
abstract：:A sensitive and specific method for the determination of chlorambucil and its metabolite in biological fluids is reported. The method is based on selected-ion monitoring detection following simple extraction of the parent compound, its metabolite, and an internal standard (chlorambucil-d8) from plasma and urine sample...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600690122
更新日期：1980-01-01 00:00:00
abstract：:This work investigates the impact of quality attributes (impurity content, plasmid charge, and compactness) of plasmid DNA isolated with different purification methodologies on the characteristics of lipoplexes prepared thereof (size, zeta potential, stability) and on their ability to transfect mammalian cells. A 3.7 ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23709
更新日期：2013-11-01 00:00:00
abstract：:A set of nonionic cellulose ethers with varying hydrophobicity and molecular weight has been investigated by principal component analysis (PCA). Several experimental variables such as dynamic surface tension, diffusion coefficient, microviscosity as monitored by a fluorescence probe technique, and intrinsic viscosity ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js9804922
更新日期：1999-08-01 00:00:00
abstract：:This article presents a theoretical model of transdermal drug delivery from an emulsion-type vehicle that addresses the vehicle heterogeneity and incorporates the prediction of drug transport parameters as function of the vehicle composition. The basic mass transfer model considers interfacial and diffusion resistance...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21268
更新日期：2008-09-01 00:00:00
abstract：:The polymorphism of rac-5,6-diisobutyryloxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF 1035) was investigated. Three different crystal forms (Form I, Form II, and Form III) were obtained by recrystallization procedures from common organic solvents. The polymorphs were characterized by Raman and ca...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.1069
更新日期：2001-08-01 00:00:00
abstract：:The objective of this study was to generate a water-soluble thiolated chitosan to enable the permeation-enhancing effect of chitosan at pH of at least 5.5 without losing the advantages of improved mucoadhesive properties. Therefore, the thiol-bearing polyoxyethylene ligand {O-(3-carboxylpropyl)-O'-[2-[3-mercaptopropio...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23832
更新日期：2014-02-01 00:00:00
abstract：:Several factors affecting the dissolution rate of cholesterol in monooctanoin were investigated. This solvent is used clinically for dissolution of residual cholesterol gallstones in the bile duct after cholecystectomy. The effect of added water on dissolution rate, measured using the static- or rotating-disk methods,...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730711
更新日期：1984-07-01 00:00:00
abstract：:A modification of wet agglomeration technique is developed and demonstrated by agglomerative crystallization process for a nonapeptide (ABT-510) to improve processing of needle like crystals. Our procedure involves exploiting partial miscibility of the crystallization solvent system for in situ generation of a wetting...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21063
更新日期：2008-03-01 00:00:00
abstract：:Effects of the commercial drug zanamivir (Relenza) covalently attached to poly-l-glutamine on the infectivity of influenza A viruses are examined using the plaque reduction assay and binding affinity to viral neuraminidase (NA). These multivalent drug conjugates exhibit (i) up to a 20,000-fold improvement in anti-infl...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22338
更新日期：2011-03-01 00:00:00
abstract：:Accelerated stability studies (37 degrees, 47 degrees, and 57 degrees) were conducted on buffered aqueous solutions (pH 7.4, 8.4, and 9.4) of hydrocortisone in the presence of various molar ratios of D-fructose. First-order degradation was observed. Significant improvement in hydrocortisone stability was seen in those...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720930
更新日期：1983-09-01 00:00:00
abstract：:The synthesis and antibacterial evaluation of a number of 2-(substituted phenylureido)-4-thiocyanatobenzothiazoles are described. The more active compounds against the test organisms in vitro generally were those substituted with halogens on the phenyl and benzothiazole rings. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670247
更新日期：1978-02-01 00:00:00
abstract：:Membrane permeation enhancers have received significant attention in recent years for enabling the oral absorption of poorly permeable drug molecules. In this study, we investigated the ability of His-Ala-Val (HAV) and Ala-Asp-Thr (ADT) peptides derived from the extracellular-1 (EC1) domain of E-cadherin proteins to i...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.12.018
更新日期：2020-12-23 00:00:00
abstract：:This study was designed to assess the effects of cooling rate, storage temperature, and formulation composition on trehalose phase distribution and protein stability in frozen solutions. The data demonstrate that faster cooling rates (>100°C/min) result in trehalose crystallization and protein aggregation as determine...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24646
更新日期：2015-12-01 00:00:00
abstract：:6-Amino-2-mercapto-5-methylpyrimidine-4-carboxylic acid proved to be a potent hypolipidemic agent in rodents at the low dose of 20 mg/kg/d. The agent effectively reduced the liver enzyme activities required for the synthesis of triglycerides and cholesterol. Lower lipid levels in tissue were observed in mice but not i...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600740713
更新日期：1985-07-01 00:00:00
abstract：:A theory of charge, fluid-mass, and solute (including macromolecular) transport through porous media is applied to describe transport phenomena across the external layer of mammalian skin. Linear relationships are derived between transport fluxes and applied fields. These relationships introduce six effective transder...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830925
更新日期：1994-09-01 00:00:00
abstract：:An alumina (Al(2)O(3))-steroid-ethanol model is used for forced degradation testing of corticosteroids to predict chemical stability and degradation products in pressurized metered-dose inhaler (pMDI) solution formulations. The model involves an ethanolic solution of a test steroid with Al(2)O(3), stressed at elevated...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23111
更新日期：2012-06-01 00:00:00
abstract：:A precursor-dependent model of indirect pharmacodynamic response which can describe tolerance and rebound was characterized in terms of the effects of changes in the fundamental properties of the drug on its response profiles. The model extends previous models by considering inhibition or stimulation of production of ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js980171q
更新日期：1998-12-01 00:00:00
abstract：:Blood levels of intact chloroprocaine were determined using a GLC procedure capable of detecting as little as 10 ng of chloroprocaine/ml of blood. It was necessary to detective plasma cholinesterases in collected samples by adding echothiophate iodide to blood sampling tubes. An extraction procedure, followed by a TLC...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600680123
更新日期：1979-01-01 00:00:00
abstract：:A sensitive and very rapid assay for acetaminophen was developed based on the combination of high-performance chromatographic columns with a thin-layer electrochemical detector. Application to liquid and solid dosage forms and body fluids has been demonstrated. Great advantage derives from the detector selectivity, wh...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640423
更新日期：1975-04-01 00:00:00
abstract：:The binding of nine diazepines to human serum albumin (HSA) and to alpha 1-acid glycoprotein (AGP) was investigated by means of fluorescence and circular dichroism (CD) spectroscopies. The binding parameters of diazepam obtained from fluorescence agreed with those obtained from CD measurements. Diazepines have one tig...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810104
更新日期：1992-01-01 00:00:00
abstract：:Under pandemic-caused emergency, evaluation of the potential of existing antiviral drugs for the treatment of COVID-19 is relevant. Triazavirin, an antiviral drug developed in Russia for per-oral administration, is involved in clinical trials against SARS-CoV-2 coronavirus. This virus has affinity to epithelial cells ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.11.016
更新日期：2020-11-26 00:00:00
abstract：:The dissolution rates of a number of drug-urethan solid-state dispersion systems were studied. A marked enhancement of the initial dissolution rates of several poorly water-soluble drugs was found when they were incorporated into a urethan matrix by heat fusion. These differences were considerable when pure substances...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670332
更新日期：1978-03-01 00:00:00
abstract：:In this study, the adsorption of an IgG1 antibody to siliconized vials was investigated with focus on the formulation parameters pH, ionic strength, and nonionic surfactants. Electrophoretic mobility measurements were performed to investigate the charge characteristics of protein and siliconized glass particles at dif...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24239
更新日期：2015-01-01 00:00:00
