Abstract：
:Solution pH and ionic strength (I) have complex effects on protein stability. We developed an experimental approach based on exploitation of the zwitterionic characteristic of amino acid molecules to probe the relative contribution from each. A variety of types of amino acid solutions were adopted to investigate the effects of pH and I in a manner that allows independent evaluation of each factor. The same effect could not be achieved using conventional buffer solutions. Size-exclusion chromatography, capillary differential scanning calorimetry, and fluorescence spectroscopy were utilized to probe the protein aggregation and conformation. The results suggested that, in addition to pH, solution ionic strength as a function of ionization state of the amino acid molecules and the ions introduced by pH adjustment played an important role in the aggregation and conformation of the protein studied. This experimental approach offers a useful tool to aid fundamental understanding of the relative effects of solution pH and ionic strength on protein stability.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Zhou R,Nashine V,Palm T,Gandhi R,Adams Mdoi
10.1002/jps.24118subject
Has Abstractpub_date
2014-10-01 00:00:00pages
3065-74issue
10eissn
0022-3549issn
1520-6017pii
S0022-3549(15)30375-0journal_volume
103pub_type
杂志文章abstract：:Three aspirin derivatives, aspirin phenylalanine ethyl ester, aspirin phenylalanine amide, and aspirin phenyllactic ethyl ester, were investigated with respect to their hydrolysis by alpha-chymotrypsin. Of the three compounds, aspirin phenylalanine ethyl ester was the best substrate, with kcat = 25 sec-1 and Km = 1.3 ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600701203
更新日期：1981-12-01 00:00:00
abstract：:In this study, injectable microspheres were developed for the local treatment of joint degeneration in rheumatoid arthritis (RA). Microspheres loaded with triamcinolone (TA), a corticosteroid drug, and/or raloxifene (Ral), a cartilage regenerative drug, were prepared with a biodegradable and biocompatible polymer, pol...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24058
更新日期：2014-08-01 00:00:00
abstract：:The remineralization behavior of weak acid-treated bovine tooth enamel has been investigated using a recently developed quantitative microradiographic method. Acetate buffer solutions at pH 4.5 containing calcium, phosphate, and 10 ppm fluoride were used in this study. When the solution ion activity product ( KFAP = a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730516
更新日期：1984-05-01 00:00:00
abstract：:To design safe, efficient synthetic gene therapy vectors, it is desirable to understand the intracellular mechanisms that facilitate their delivery from the cell surface to the nucleus. Elements of the cytoskeleton and molecular motor proteins are known to play a pivotal role in most intracellular active transport pro...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21106
更新日期：2008-04-01 00:00:00
abstract：:In a continuing search for new biologically active agents derived from indolizine, 3-(2-aminoethyl)-2-methylindolizine, 3-(2-aminoethyl)-2-methyl-5,6,7,8-tetrahydroindolizine, and some mono- and di-N-substituted derivatives were prepared. Initial pharmacological screening showed that these compounds possess anti-5-hyd...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600680317
更新日期：1979-03-01 00:00:00
abstract：:Pretreatment with cyclosporine reportedly prolongs the effect of certain general anesthetics in humans and the sleeping time of mice after pentobarbital administration. This investigation was designed to determine the mechanism(s) of the cyclosporine-barbiturate interaction. Adult female Wistar rats received cyclospor...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600790106
更新日期：1990-01-01 00:00:00
abstract：:The delivery of drugs via the mucous membranes lining the oral cavity (i.e., sublingual and buccal), with consideration of both systemic delivery and local therapy, is reviewed in this paper. The structure and composition of the mucosae at different sites in the oral cavity, factors affecting mucosal permeability, pen...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.2600810102
更新日期：1992-01-01 00:00:00
abstract：:Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a r...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20484
更新日期：2006-01-01 00:00:00
abstract：:3D cultures of primary human hepatocytes (PHH) are emerging as a more in vivo-like culture system than previously available hepatic models. This work describes the characterisation of drug metabolism in 3D PHH spheroids. Spheroids were formed from three different donors of PHH and the expression and activities of impo...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.10.043
更新日期：2021-01-01 00:00:00
abstract：:This article discusses the evaluation of drug candidates as hepatic transporter substrates. Recently, research on the applications of hepatic transporters in the pharmaceutical industry has improved to meet the requirements of the regulatory guidelines for the evaluation of drug interactions. To identify the risk of t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1016/j.xphs.2017.05.009
更新日期：2017-09-01 00:00:00
abstract：:An automated two-phase method for the simultaneous fluorometric determination of the spironolactone metabolites canrenone (II) and canrenoic acid (III) in serum is described. The determination is performed by two dichloroethane extractions of the same serum sample at different pH values. The fluorescence developed in ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660820
更新日期：1977-08-01 00:00:00
abstract：:One manifestation of cystic fibrosis (CF) is the presence of a viscid mucus secretion in the lungs. The clearance of this mucus is significantly slower than in "normals" due to uncoordinated beating of the cilia and the increased viscosity of the mucus. In these studies, the permeabilities of p-aminosalicylic acid, is...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js950381s
更新日期：1996-06-01 00:00:00
abstract：:Anionic surfactants compromise skin's barrier function by damaging stratum corneum lipids and proteins. The objective of this study was to examine anionic surfactant-induced changes in the skin's polar and transcellular pathways and the resulting impact on surfactant penetration into the skin. Three anionic surfactant...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.06.030
更新日期：2019-11-01 00:00:00
abstract：:This work compares the conformational stability, backbone flexibility, and aggregation propensity of monomer and dimer fractions of an IgG1 monoclonal antibody (mAb) generated on UVA light exposure for up to 72 h collected by preparative size-exclusion chromatography, compared with unstressed control. UVA light exposu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.01.017
更新日期：2018-06-01 00:00:00
abstract：:An immune response for a nasal ovalbumin (OVA) powder formulation with an applied nasal delivery platform technology, consisting of a powdery nasal carrier and a device, was evaluated in monkeys with similar upper respiratory tracts and immune systems to those of humans, in order to assess the applicability to a vacci...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.11.023
更新日期：2020-12-03 00:00:00
abstract：:It is shown that the existence of the second peak on the drug plasma concentration time curve C(p)(t) after iv bolus dosing can be explained by considering the traditional multi-compartmental linear pharmacokinetics. It was found that a direct solution of the general three-compartment model yields the second peak of C...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21151
更新日期：2008-06-01 00:00:00
abstract：:The purpose of the study was to characterize mucosal attachment of a cationized model protein, bovine serum albumin (BSA), onto the various fractions of colonic crypts epithelium in the rat. BSA was labeled with fluorescein isothiocyanate (FITC) and its surface net electric charge was modified from negative to positiv...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.1102
更新日期：2001-10-01 00:00:00
abstract：:Various complex mechanisms and their multifactorial pathways decisively provoke low-grade local and systemic inflammation in β-cells of pancreatic islets and peripheral tissues to induce β-cells' dysfunction and apoptosis, insulin resistance, and ultimately, overt type 2 diabetes mellitus (T2DM). Conventional antidiab...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.23057
更新日期：2012-05-01 00:00:00
abstract：:Alkyl esters of ketorolac were synthesized as potential prodrugs for transdermal delivery and evaluated to determine the relationship between their skin permeation characteristics and their physicochemical properties. Solubility of the prodrugs in various vehicles was determined at room temperature while lipophilicity...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10353
更新日期：2003-05-01 00:00:00
abstract：:The particle sizing performance of a Next Generation Pharmaceutical Impactor (NGI) was compared to that of an Andersen cascade impactor (ACI). A single lot of Vanceril MDIs containing beclomethasone dipropionate (BDP) was used throughout. MDIs were sampled into NGI and ACI in accordance with USP recommendations, at 30...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20091
更新日期：2004-07-01 00:00:00
abstract：:The chemical stability of the novel anticancer agent carzelesin in aqueous buffer/acetonitrile (1:1, v/v) mixtures has been investigated utilizing a stability-indicating reversed-phase high-performance liquid chromatographic assay. The degradation kinetics of carzelesin has been studied as a function of pH, buffer com...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js960005n
更新日期：1996-11-01 00:00:00
abstract：:Previous studies from this laboratory suggested that a solution model (Flory-Huggins equation) modified by a free volume model (Vrentas equation) could satisfactorily describe water absorption into an amorphous solid composed of a sugar or a polymer. This paper has extended the studies of single solutes to binary mixt...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.1090
更新日期：2001-09-01 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 rapid, sensitive, and accurate reversed-phase HPLC method has been developed for the analysis and quantification of pharmaceutical formulations containing tyrothricin (1), an antibiotic used in antiseptic buccal compressed tablets for local application. The assay has been carried out under isocratic conditions, usin...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830815
更新日期：1994-08-01 00:00:00
abstract：:The objective of this study was to investigate the permeation-enhancing effect of thiolated polycarbophil (PCP) on peptide drugs. Mediated by a carbodiimide, increasing amounts of cysteine (Cys) were covalently bound to sodium neutralized PCP (NaPCP). The extent of covalently attached Cys was determined by quantifying...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/1520-6017(200010)89:10<1253::aid-jps3>3.0.
更新日期：2000-10-01 00:00:00
abstract：:The use of enzymes as therapeutics is very promising because of their catalytic activity and specificity. However, intracellular delivery of active enzymes is challenging due to their low stability and large size. The production of protein-enzyme nanoparticles was investigated with the goal of developing a protein car...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23974
更新日期：2014-06-01 00:00:00
abstract：:Intravenously administered (i.v.) drug-cyclodextrin (CD) inclusion complexes are generally expected to dissociate rapidly and completely, such that the i.v. pharmacokinetic profile of a drug is unchanged in the presence of CD. The altered pharmacokinetics of a synthetic ozonide in rats has been attributed to an unusua...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24331
更新日期：2015-04-01 00:00:00
abstract：:A new synthesis is described for 10alpha-methoxy-delta8,9-lysergaldehyde involving the oxidation of elymoclavine with manganese dioxide in methanol. Lysergol and agroclavine provide no reaction under the same conditions. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660937
更新日期：1977-09-01 00:00:00
abstract：:Flexible manufacturing technologies for solid oral dosage forms with a continuous adjustability of the manufactured dose strength are of interest for applications in personalized medicine. This study explored the feasibility of using microvalve technology for the manufacturing of different solid oral dosage form conce...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.11.007
更新日期：2018-03-01 00:00:00
abstract：:Human skin samples are permeable to theophylline delivered from 1.5% solutions in various alkanecarboxylic acids and their mixtures. The respective permeability coefficients of theophylline, calculated from steady-state flux, correlate negatively with the permeability coefficients of the donor carboxylic acids and pos...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600761004
更新日期：1987-10-01 00:00:00
