Abstract：
:It is now becoming apparent that a common pathway of protein aggregation involves the unimolecular structural rearrangement from the native state to a slightly expanded aggregation-competent species. It is the goal of this study to understand the aggregation and the effects of buffer on the stability of IFN-tau. In this study, the thermally-induced aggregation of interferon-tau (IFN-tau) is described. By monitoring the aggregation rate in the presence of increasing amounts of sucrose, the relative change in surface area (Deltas) for conversion to the aggregation-competent state can be determined. Under conditions of pH 7 and in 20 mM buffer, the protein displays different aggregation rates depending on the nature of the buffer species. The protein aggregates mostly quickly in phosphate buffer, slower in the presence of Tris and slowest in the presence of histidine. The largest value for Deltas occurs for the histidine-containing samples, where aggregation proceeds via a slightly expanded aggregation competent state with a surface area increase of 7.6%. Furthermore, it appears that histidine binds to the native state of IFN-tau, thereby stabilizing the native state and retarding aggregation. Measurement of the second virial coefficient, B(22), for different formulations indicates that inclusion of histidine has only a small effect on repulsion between protein molecules, suggesting that colloidal stabilization is not the dominant mechanism for stabilization of IFN-tau. This study represents the first detailed biophysical study of specific buffer-induced stabilization, resulting in shifting the equilibrium towards the native state and away form the expanded aggregation-competent species.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Katayama DS,Nayar R,Chou DK,Valente JJ,Cooper J,Henry CS,Vander Velde DG,Villarete L,Liu CP,Manning MCdoi
10.1002/jps.20471subject
Has Abstractpub_date
2006-06-01 00:00:00pages
1212-26issue
6eissn
0022-3549issn
1520-6017pii
S0022-3549(16)32027-5journal_volume
95pub_type
杂志文章abstract：:The skin penetration of 10 nonsteroidal antiinflammatory drugs (NSAIDs) was investigated after application in the lipophilic vehicle light mineral oil. The skin permeabilities and maximum fluxes, which were calculated from the concentration decreases of the applied solutions in the steady state phases, were correlated...
journal_title：Journal of pharmaceutical sciences
pub_type： 临床试验,杂志文章
doi：10.1021/js990032o
更新日期：1999-12-01 00:00:00
abstract：:Nonionic surfactants (caprylocaproyl macrogol-8 glycerides, octoxynol-12, polysorbate-20, and polyethylene glycol-40 hydrogenated castor oil) (47.03%, w/w), costabilizer (poloxamer 407) (12%-20%, w/w), oil (isopropyl myristate) (5.22%, w/w), water (q.s. ad 100%, w/w), and ibuprofen (5%, w/w) were used to develop oil-i...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24494
更新日期：2015-08-01 00:00:00
abstract：:The comparative pharmacokinetics of free MTP-PE (muramyl tripeptide phosphatidyl ethanolamine) and MTP-PE entrapped in negatively charged multilamellar liposomes (liposomal MPT-PE) was evaluated in rats at a bolus intravenous (i.v.) dose of 0.2 mg/kg and in dogs at a bolus i.v. dose of 0.1 mg/kg. Additional studies we...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600821005
更新日期：1993-10-01 00:00:00
abstract：:In this work, a novel risk-based methodology for lot release is proposed. Its objective is to assess the risk that a lot declared to have passed truly meets product specifications. The methodology consists of 3 parts: adaptive sample size determination, estimation of the probability that the product was within specifi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.10.011
更新日期：2020-02-01 00:00:00
abstract：:The ratio between ocular and systemic drug concentrations describes the relative safety of ophthalmic dosage forms of the same drug in terms of its systemic side effects. In this study, we evaluated the effects of epinephrine pretreatment and solution pH on the aqueous humor:plasma and iris-ciliary body:plasma ratios ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600790808
更新日期：1990-08-01 00:00:00
abstract：:Angiogenesis--process of new blood-vessel growth from existing vasculature--is an integral part of both normal developmental processes and numerous pathologies such as cancer, ischemic diseases and chronic inflammation. Angiogenesis plays a crucial role facilitating tumour growth and the metastatic process, and it is ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.21286
更新日期：2008-10-01 00:00:00
abstract：:Systematic structural modifications were performed on the natural sesquiterpene lactone tenulin to define those groupings essential to, or significant in, its in vivo antitumor activity. Accordingly, the following tenulin analogs were prepared: dihydrotenulin, 2,3-epoxytenulin, isotenulin, dihydroisotenulin, 2,3-epoxy...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600680616
更新日期：1979-06-01 00:00:00
abstract：:An on-line, high-performance frontal analysis (HPFA)-high-performance liquid chromatographic system was developed for the enantioselective determination of a low level of unbound ketoprofen (KP) that is in equilibrium with KP that is bound to protein. The system consists of three subsystems (HPFA system, preconcentrat...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810725
更新日期：1992-07-01 00:00:00
abstract：:Methods for monitoring mechanical events occurring within particulate solids systems in a dynamic state are described. The electrical conductance and capacitance characteristics of such systems, as they relate to the degree of bed dilation or expansion, extent of interparticulate contact, and intensity of particle mot...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670825
更新日期：1978-08-01 00:00:00
abstract：:Quantitative applications for pharmaceutical solid dosage forms using near-infrared (NIR) spectroscopy are central to process analytical technology (PAT) manufacturing designs. A series of studies were conducted to evaluate the use of NIR transmission mode under various pharmaceutical settings. The spectral variabilit...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21777
更新日期：2009-12-01 00:00:00
abstract：:Intranasal delivery of flurazepam, midazolam, and triazolam was studied in a dog model as a possible alternate route of drug administration for treatment of insomnia. Four beagles received each hypnotic by both intranasal and oral routes on two separate occasions. Plasma concentrations for each hypnotic after dosing w...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600801207
更新日期：1991-12-01 00:00:00
abstract：:Tablet characteristics of tensile strength and disintegration time were predicted using residual stress distribution, simulated by the finite element method (FEM). The Drucker-Prager Cap (DPC) model was selected as the method for modeling the mechanical behavior of pharmaceutical powders composed of lactose (LAC), cor...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23675
更新日期：2013-10-01 00:00:00
abstract：:Pharmaceutical scientists are often asked to assess the impact of modifications to the illumination in the manufacturing and product packaging environment on product quality. To assess the impact of switching light sources, four model compounds were exposed to standard fluorescent light, LED, and "yellow light" and th...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.07.020
更新日期：2020-11-01 00:00:00
abstract：:The in vitro binding of warfarin by human serum albumin was studied at various temperatures and at pH 7.4 by a frontal gel filtration technique. The results can be best described in terms of a two class-of-binding site model, in which the numbers of primary and secondary sites are constrained to the average values for...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600651127
更新日期：1976-11-01 00:00:00
abstract：:A fluorescence method is presented for the determination of nitrofurantoin based on conversion of the drug to a fluorescent substance. The method requires 0.1-0.5 ml of plasma or diluted urine and is 10 times more sensitive than the commonly used colorimetric method. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600690134
更新日期：1980-01-01 00:00:00
abstract：:Quantitative determination of serum concentrations of carvedilol [(+/-)-1-(carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl) amino]-2-propanol], a combined alpha- and beta-adrenergic receptor antagonist, was obtained using HPLC with spectrofluorometric detection. Carvedilol was extracted from alkalinized serum with eth...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600751218
更新日期：1986-12-01 00:00:00
abstract：:The aim of this study was to characterize the in vitro hepatic uptake kinetics of sodium fluorescein (NaFluo) and identify the transporters involved. NaFluo exhibited saturable uptake kinetics in suspended rat and human hepatocytes as reflected by K(m) values of 22.5 and 14.1 µM, and V(max) values of 98.3 and 5.8 pmol...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22694
更新日期：2011-11-01 00:00:00
abstract：:To prepare (+)-tubocurine and O,O-dimethyl-(+)-tubocurine, the commonly used dequaternization procedures with sodium theophenoxide and ethanolamine were investigated. The quaternary compounds were (+)-tubocurarine chloride and the chloride and iodide salts of O,O-dimethyl-(+)-chondocurarine. The results obtained with ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670904
更新日期：1978-09-01 00:00:00
abstract：:Daunorubicin (DAUN) and doxorubicin (DOX) are used to treat a variety of cancers. The use of DAUN and DOX is hampered by the development of cardiotoxicity. Clinical evidence suggests that patients with leukemia and Down syndrome are at increased risk for anthracycline-related cardiotoxicity. Carbonyl reductases and al...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.03.013
更新日期：2016-06-01 00:00:00
abstract：:Solubilization of nonpolar drugs constitutes one of the most important tasks in parenteral formulations design. This study investigates and assesses the solubility enhancement of Fluasterone by various techniques including cosolvency, micellization, and complexation. Of the solubilizing agents used, the modified beta-...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js9901413
更新日期：1999-10-01 00:00:00
abstract：:6-Chloro-9-[2-(6-methyl-3-pyridyl)ethyl]-1,2,3,4-tetrahydrocarbazole-2-carboxylic acid hydrochloride lowered serum cholesterol, triglyceride, phospholipid, and free fatty acid levels in normal rats. The compound appeared to have a low toxicity and to be well tolerated in mice, adult and neonatal rats, and rabbits. At ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660311
更新日期：1977-03-01 00:00:00
abstract：:In relation to drug release properties the lateral and rotational mobility of two drugs and one drug mimic in photopolymerized poly(ethylene glycol) diacrylate (PEGDA) networks were investigated by nuclear magnetic resonance as a function of the network cross-link density and temperature. The network mesh size affects...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21251
更新日期：2008-08-01 00:00:00
abstract：:A rapid, sensitive, and specific determination of ketoprofen in human and animal deproteinized body fluids by reversed-phase high-pressure liquid chromatography is presented. The acid is detectable in amounts as low as 0.1 microgram/ml. Limits of error are in the range of +/- 5.1% of the sample mean. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600680330
更新日期：1979-03-01 00:00:00
abstract：:Protein and peptide antigens frequently are only slightly immunogenic when utilized alone in vaccines. Formulation of these antigens in a carrier vehicle, particularly when an adjuvant is included, often results in markedly enhanced immune responses. Encapsulation of peptide and protein antigens in liposomes generally...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js9601593
更新日期：1996-12-01 00:00:00
abstract：:The increased incidence of human immunodeficiency virus infection in women has identified an urgent need to develop a female-controlled method to prevent acquisition of human immunodeficiency virus and other sexually transmitted diseases. Women would apply the product intravaginally before intercourse. Development of ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20107
更新日期：2004-08-01 00:00:00
abstract：:The bioavailability of clofibric acid from formulations containing calcium clofibrate along and mixed with calcium carbonate (1:1 w/w) was compared to that from a standard clofibrate formulation in a crossover study in 12 human subjects. The 95% confidence intervals of bioavailability differences were such that they ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600661138
更新日期：1977-11-01 00:00:00
abstract：:Results of studies carried out in rats for model compounds, D-(-) mandelic acid, benzoylformic acid, and some of their para-alkylated homologs, showed that their biological half-lives determined from the elimination phase of urinary excretion data were longer than those determined from the elimination phase of blood l...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650920
更新日期：1976-09-01 00:00:00
abstract：:Hydroxypropyl cellulose films were prepared by compression molding of three different lots of hydroxypropyl cellulose powder at 149 degrees C, 188 degrees C, and 232 degrees C. Rectangular pieces were cut from these films and viscosity average molecular weight (Mv), degree of orientation, and rate of dissolution were ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600740509
更新日期：1985-05-01 00:00:00
abstract：:The described simple, accurate, and precise reversed-phase high-pressure liquid chromatographic procedure is in excellent agreement with 1-octanol shake-flask partition or distribution coefficients over a 3.5 log range. A chemically bonded octadecylsilane support is persilated and coated with 1-octanol. With 1-octanol...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600671008
更新日期：1978-10-01 00:00:00
abstract：:Avoiding unwanted immunogenicity is of key importance in the development of therapeutic drug proteins. Animal models are of less predictive value because most of the drug proteins are recognized as foreign proteins. However, different methods have been developed to obtain immunotolerant animal models. So far, the immu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23447
更新日期：2013-03-01 00:00:00
