Abstract：
:The stability of two purified monoclonal antibodies, MN12 and WT31, was investigated. The monoclonal antibodies were incubated for 32 days at different pH values (ranging from 3.0 to 10.0) at 4 and 37 degrees C. Various analytical methods were used to assess changes in physicochemical properties of the proteins. The monoclonal antibodies were more susceptible to degradation at 37 degrees C than at 4 degrees C. At low pH irreversible precipitation occurred. Decomposition of the proteins was enhanced at increasing pH values in the alkaline range. This was concluded from mouse IgG-specific and antigen-specific enzyme-linked immunosorbent assays, flow cytometry, analytical gel permeation chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, and immunoblotting. No substantial change in the apparent affinity constant of MN12 was observed, as determined by an affinity enzyme-linked immunosorbent assay. Fluorescence spectra, fluorescence polarization values, and fluorescence quenching parameters of MN12 and WT31 were not substantially affected, indicating that no major irreversible conformational changes had occurred. It was concluded that each of the techniques used has only limited value for stability assessment of monoclonal antibodies and, hence, that the application of several analytical techniques is essential to gain insight into monoclonal antibody stability.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Jiskoot W,Beuvery EC,de Koning AA,Herron JN,Crommelin DJdoi
10.1023/a:1015925519154subject
Has Abstractpub_date
1990-12-01 00:00:00pages
1234-41issue
12eissn
0724-8741issn
1573-904Xjournal_volume
7pub_type
杂志文章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：PURPOSE:The aim of the present study was to improve the dry powder inhalation behavior of steroid KSR-592 with lactose by altering the crystal shape and the particle size of the drug for use in a newly designed inhalation device, Jethaler. METHOD:The shape of the crystals was changed by polymorphic transformation of o...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020492213172
更新日期：2002-10-01 00:00:00
abstract：PURPOSE:To develop a semi-distributed liver model for the evaluation of saturable sinusoidal uptake and binding kinetics of the Oatp1a4 substrate digoxin. METHODS:In the perfused rat liver, two successive digoxin doses of 42 and 125 microg were administered, and the outflow concentration was determined by LC/MS/MS. [1...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0204-9
更新日期：2010-09-01 00:00:00
abstract：PURPOSE:Some patients are unable to generate the peak inspiratory flow rate (PIFR) necessary to de-agglomerate drug particles from dry powder inhalers (DPIs). In this study we tested the hypothesis that the acoustic parameters of an inhalation are related to the PIFR and hence reflect drug delivery. METHODS:A sensitiv...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1371-x
更新日期：2014-10-01 00:00:00
abstract：PURPOSE:Tumor vascular normalization by antiangiogenic agents may increase tumor perfusion but reestablish vascular barrier properties in CNS tumors. Vascular priming via nanoparticulate carriers represents a mechanistically distinct alternative. This study investigated mechanisms by which sterically-stabilized liposom...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0823-4
更新日期：2012-12-01 00:00:00
abstract：:A novel method of dipeptide synthesis is described that can be carried out in aqueous solution and does not require complicated protecting and deprotecting procedures. An analgesic neuropeptide named kyotorphin, H-Tyr-Arg-OH, was synthesized from unprotected tyrosine and arginine in a new enzymatic reaction catalyzed ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016479305603
更新日期：1987-04-01 00:00:00
abstract：:Lecithin-stabilized triglyceride emulsions are subject to hydrolysis by pancreatic lipase. The time profiles of these reactions are characterized by a lag-phase and a zero-order phase. Lag phases are more pronounced with long-chain triglycerides. Ca2+ is effective in reducing the lag-phase and activating lipase. Kinet...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015956104500
更新日期：1989-06-01 00:00:00
abstract：PURPOSE:In this study, we aimed to illustrate the utility of fractional radiofrequency (RF) that generated microchannels in the skin, allowing delivery of peptide and siRNA via the skin. The mechanisms involved in the correlation between macromolecule permeation and skin structure were also elucidated. METHODS:The mor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1568-z
更新日期：2015-05-01 00:00:00
abstract：PURPOSE:The purpose of this human intestinal perfusion study was to investigate the transport and metabolism of R/S-verapamil in the human jejunum (in vivo). METHODS:A regional single-pass perfusion of the jejunum was performed using a Loc-I-Gut perfusion tube in 12 healthy volunteers. Each perfusion lasted for 200 mi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011916329863
更新日期：1998-06-01 00:00:00
abstract：PURPOSE:Changes in drug absorption and first-pass metabolism have been reported throughout the pediatric age range. Our aim is to characterize both intestinal and hepatic CYP3A-mediated metabolism of midazolam in children in order to predict first-pass and systemic metabolism of CYP3A substrates. METHODS:Pharmacokinet...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2458-6
更新日期：2018-07-30 00:00:00
abstract：PURPOSE:The aim of the present study was to design a new mucosal drug delivery system composed of liposomes dispersed within a bioadhesive hydrogel containing methyl-beta-cyclodextrin (Me(beta)CD) for controlled drug release. METHODS:A hydrophilic model molecule, inulin, was encapsulated within positively charged and ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-4591-2
更新日期：2005-06-01 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：:Apigenin, a naturally occurring plant flavone, abundantly present in common fruits and vegetables, is recognized as a bioactive flavonoid shown to possess anti-inflammatory, antioxidant and anticancer properties. Epidemiologic studies suggest that a diet rich in flavones is related to a decreased risk of certain cance...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-010-0089-7
更新日期：2010-06-01 00:00:00
abstract：PURPOSE:To assess the efficacy of lipid-protein-sugar particles (LPSPs) in providing prolonged duration local anesthesia by percutaneous injection. METHODS:Bupivacaine-containing LPSPs were characterized and optimized in vitro. Male Sprague-Dawley rats were given sciatic nerve blocks with bupivacaine-containing LPSPs....
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1026470831256
更新日期：2000-10-01 00:00:00
abstract：PURPOSE:To evaluate and classify the hydrolases of the primate lung. METHODS:Homologous series of aromatic, aliphatic, and choline ester substrates were assayed with the pH-stat method to obtain the Michaelis-Menten kinetic constants, Vmax and K(m), for the enzymes in pulmonary alveolar tissue with esterase activity. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012004911942
更新日期：1997-02-01 00:00:00
abstract：PURPOSE:To design and synthesize fatty acid-RGD peptide amphiphiles with ADA linker for their potential delivery of hydrophobic drugs like paclitaxel targeted to α(v)β(3) integrin overexpressing tumors. METHODS:Four amphiphiles - C16 or C18 fatty acid-RGD peptide and ADA linker were designed and synthesized. CMC, size...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0830-5
更新日期：2012-12-01 00:00:00
abstract：:Magnetic nanoparticles are useful as contrast agents for magnetic resonance imaging (MRI). Paramagnetic contrast agents have been used for a long time, but more recently superparamagnetic iron oxide nanoparticles (SPIOs) have been discovered to influence MRI contrast as well. In contrast to paramagnetic contrast agent...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-012-0711-y
更新日期：2012-05-01 00:00:00
abstract：:The pharmacokinetics of and biologic response modification by recombinant human interferon-beta ser (rIFN-beta ser) were evaluated in 12 healthy male volunteers. Subjects received a single intravenous (iv) injection of 90 x 10(6) IU of rIFN-beta ser followed by a single or eight consecutive daily 90 x 10(6) IU subcuta...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018902120023
更新日期：1993-04-01 00:00:00
abstract：:The effect of the penetration enhancers Azone, oleic acid, 1-dodecanol, dodecyl N,N-dimethylaminoacetate (DDAA), and dodecyl N,N-dimethylaminoisopropionate (DDAIP) on epithelial membrane lipids was examined using human buccal cell membranes as a model for epithelial lipid bilayer. Buccal epithelial cells (BEC) were la...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018919811227
更新日期：1994-02-01 00:00:00
abstract：PURPOSE:The major objectives of this study were to 1) develop a new mathematical model describing all phases of drug release from bioerodible microparticles; 2) evaluate the validity of the theory with experimental data; and 3) use the model to elucidate the release mechanisms in poly(lactide-co-glycolide acid)-based m...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1021457911533
更新日期：2002-12-01 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:To study the oxidative degradation of drugs using a hydrophilic free radical initiator, 2,2'-Azobis(-amidinopropane) dihydrochloride (AAPH). METHODS:AAPH was used as the free radical initiator to study oxidation of three model compounds (A, B, and C), which represent different oxidizable moieties. In the solut...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-1199-x
更新日期：2005-02-01 00:00:00
abstract：PURPOSE:Anticancer chemotherapy usually involves the administration of several anticancer drugs that differ in their action mechanisms. Here, we aimed to test whether the combination of omacetaxine mepesuccinate (OMT) and doxorubicin (DOX) could show synergism, and whether the liposomal co-delivery of these two drugs c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1317-3
更新日期：2014-08-01 00:00:00
abstract：:An empirical mass-transfer model for enteric-coating dissolution that uses in vivo dissolution data to characterize the pH-dependent solubility properties of the polymer film and a mass-transfer coefficient determined from in vivo dissolution or disintegration studies is developed. Once the in vivo mass-transfer coeff...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018986827350
更新日期：1993-02-01 00:00:00
abstract：PURPOSE:To develop an efficient tumor vasculature-targeted polymeric micelle delivery system for combretastatin A4 (CA4), a novel antivascular agent. METHODS:CA4-loaded micelles were prepared from poly (ethylene glycol)-b-poly (d, l-lactide) copolymers. RGD peptides that target integrins alphavbeta3 and alphavbeta5, m...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0184-9
更新日期：2010-09-01 00:00:00
abstract：PURPOSE:The present study evaluates immobilized artificial membrane (IAM) chromatography for predicting drug permeability across the blood-brain barrier (BBB) and outlines the potential and limitations of IAMs as a predictive tool by comparison with conventional methods based on octanol/water partitioning and octadecyl...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011904311149
更新日期：1998-08-01 00:00:00
abstract：:One thousand milligrams of aspirin, as its lysine salt was administered intravenously, orally, and intramuscularly to nine male and nine female young healthy adult volunteers. After intravenous injection mean (+/- SD) values of clearance, steady-state volume of distribution, and terminal half-life were 12.2 +/- 2.2 ml...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章
doi：10.1023/a:1015978104017
更新日期：1989-08-01 00:00:00
abstract：PURPOSE:To investigate the effect of γ-irradiation of poly(lactic-co-glycolic acid) (PLGA)/Al(OH)₃/0 or 5 wt% diethyl phthalate (DEP) microspheres for active self-healing encapsulation of vaccine antigens. METHODS:Microspheres were irradiated with ⁶⁰Co at 2.5 and 1.8 MRad and 0.37 and 0.20 MRad/h. Encapsulation of tet...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1019-2
更新日期：2013-07-01 00:00:00
abstract：PURPOSE:Overexpression of the serine protease urokinase (uPA) is recognised as an important biomarker of metastatic disease and a druggable anticancer target. Plasminogen activator inhibitor type-2 (PAI-2/SerpinB2) is a specific uPA inhibitor with proven potential for use in targeted therapy. However, PAI-2 is rapidly ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1517-x
更新日期：2015-03-01 00:00:00
abstract：PURPOSE:To determine whether LHRH-receptor is expressed in Calu-3, a human bronchial epithelial cell line, and to further determine whether this receptor plays a role in the transport of deslorelin, an LHRH agonist. METHODS:Using cultured monolayers of Calu-3 grown at air-interface, the presence and localization of LH...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000029294.70707.74
更新日期：2004-06-01 00:00:00
