Abstract：
PURPOSE:Studies were conducted to investigate dilute solutions of the monoclonal antibody (mAb) bevacizumab, mAb fragment ranibizumab and fusion protein aflibercept, develop common procedures for formulation of low concentration mAbs and identify a stabilizing formulation for anti-VEGF mAbs for use in in vitro permeation studies. METHODS:Excipient substitutions were screened. The most stabilizing formulation was chosen. Standard dilutions of bevacizumab, ranibizumab and aflibercept were prepared in PBS, manufacturer's formulation, and the new formulation. Analysis was by SE-HPLC and ELISA. Stability, disaggregation and pre-exposure tests were studied. RESULTS:When Avastin, Lucentis and Eylea are diluted in PBS or manufacturer's formulation, there is a 40-50% loss of monomer concentration and drug activity. A formulation containing 0.3% NaCl, 7.5% trehalose, 10 mM arginine and 0.04% Tween 80 at a pH of 6.78 stabilized the mAbs and minimized the drug loss. The formulation also disaggregates mAb aggregation while preserving the activity. Degassing the formulation increases recovery. CONCLUSIONS:We developed a novel formulation that significantly stabilizes mAbs under unfavorable conditions such as low concentration or body temperature. The formulation allows for tissue permeation experimentation. The formulation also exhibits a disaggregating effect on mAbs, which can be applied to the manufacture/packaging of mAbs and bioassay reagents.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Giannos SA,Kraft ER,Zhao ZY,Merkley KH,Cai Jdoi
10.1007/s11095-018-2368-7subject
Has Abstractpub_date
2018-02-28 00:00:00pages
78issue
4eissn
0724-8741issn
1573-904Xpii
10.1007/s11095-018-2368-7journal_volume
35pub_type
杂志文章abstract：PURPOSE:Knowledge about the uptake mechanism and subsequent intracellular routing of non-viral gene delivery systems is important for the development of more efficient carriers. In this study we compared two established cationic polymers pDMAEMA and PEI with regard to their transfection efficiency and mechanism of cell...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9287-3
更新日期：2007-08-01 00:00:00
abstract：PURPOSE:To develop an enzymatically-controlled pulsatile drug release system based on an impermeable capsule body, which contains the drug and is closed by an erodible pectin/pectinase-plug. METHODS:The plug was prepared by direct compression of pectin and pectinase in different ratios. In addition to the disintegrati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018959327311
更新日期：1999-09-01 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：:The synthesis of an homologous series of new water-soluble derivatives of pilocarpine is described. The new compounds, referred to as soft quaternary salts, are water soluble by virtue of a cationic ammonium head and their lipophilicity can be modulated by manipulating the size and the nature of the substituent in the...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015847103862
更新日期：1992-03-01 00:00:00
abstract：:Loracarbef is an oral 1-carba-1-dethiacephalosporin antibiotic structurally related to cefaclor. Like many beta-lactam antibiotics, loracarbef exists in several hydrated crystalline forms. The pH-solubility profile curve for loracarbef monohydrate is U-shaped, resembling those of other zwitterionic cephalosporins. Lor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018949709797
更新日期：1992-02-01 00:00:00
abstract：PURPOSE:A thermodynamic analysis of the binding to rat cortex adenosine A1 receptor of N6-substituted (full agonists) and N6-substituted-deoxyribose (partial agonists) adenosine derivatives was performed. The intrinsic activity of the compounds was evaluated by measurements of the inhibition of forskolin stimulated 3',...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018987816891
更新日期：1999-07-01 00:00:00
abstract：PURPOSE:To study the biorelevant drug release from novel starch-based polyvinyl alcohol capsules (S-PVA-C). The effect of the shell material is studied by considering microstructural formulation changes during hydration. METHODS:Two different self-emulsifying systems containing either fenofibrate or probucol were fill...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1152-y
更新日期：2014-01-01 00:00:00
abstract：PURPOSE:To compare the permeation characteristics of amide bond-containing HIV-1 protease inhibitors and their pyrrolinone-containing counterparts across Caco-2 cell monolayers, a model of the intestinal mucosa. METHODS:Transepithelial transport and cellular uptake of three pairs of amide bond-containing and pyrrolino...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011966918959
更新日期：1998-05-01 00:00:00
abstract：:The limitations of traditional gas adsorption models for describing water vapor sorption by amorphous pharmaceutical solids are described and an alternative approach based on polymer solution theories is proposed. The approach is tested by comparing a priori predicted isotherms with literature data for the poly(vinylp...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018901325842
更新日期：1993-09-01 00:00:00
abstract：PURPOSE:The aim of this study was to investigate transepithelial ionic permeation via the paracellular pathway of human Caco-2 epithelial monolayers and its contribution to absorption of the base guanidine. METHODS:Confluent monolayers of Caco-2 epithelial cells were mounted in Ussing chambers and the transepithelial ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9568-2
更新日期：2006-03-01 00:00:00
abstract：PURPOSE:Poly-L-arginine (PLA) enhances the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules by disappearance of tight junction (TJ) proteins from cell-cell junctions. However, the mechanism of the disappearance of TJ proteins in response to PLA has been unclear. In this study, we inv...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1324-4
更新日期：2014-09-01 00:00:00
abstract：:The interdependent relationship between pharmacology and toxicology is fundamental to the concepts of efficacy and safety of both drugs and xenobiotics. The traditional concept of establishing efficacious and tolerated doses to define a 'therapeutic window' appears simplistic in the context of an exponentially increas...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-014-1415-2
更新日期：2014-09-01 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: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:The fate of inhaled salmon calcitonin (sCT) at the respiratory epithelial barrier was studied with particular emphasis on enzymatic degradation by trypsin, chymotrypsin, and neutrophil elastase. METHODS:Degradation of sCT was assessed by HPLC in cell homogenate, supernatant and intact monolayers of human respi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0553-z
更新日期：2012-01-01 00:00:00
abstract：:A novel floating controlled-release drug delivery system was formulated in an effort increase the gastric retention time of the dosage form and to control drug release. The buoyancy was attributed to air and oil entrapped in the agar gel network. A floating controlled-release 300-mg theophylline tablet having a densit...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018921830385
更新日期：1993-09-01 00:00:00
abstract：PURPOSE:The aim was to design and thoroughly characterize monodisperse Fe3O4@SiO2-Ag nanoparticles with strong antibacterial properties, which makes them a candidate for targeting bacterial infections. METHODS:The monodisperse Fe3O4 nanoparticles were prepared by oleic acid-stabilized thermal decomposition of Fe(III) ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2680-x
更新日期：2019-08-14 00:00:00
abstract：PURPOSE:To characterize the uptake mechanism of zidovudine (AZT), a nucleoside reverse transcriptase inhibitor, in syncytiotrophoblast cells using the TR-TBT 18d-1 cell line previously established by our group. MATERIALS AND METHODS:The effects of several transporter inhibitors on the initial and steady-state apical u...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9564-9
更新日期：2008-07-01 00:00:00
abstract：PURPOSE:Gastrointestinal deposition of nanoparticles was examined after oral administration to mice suffering from an experimental gastric ulcer model. Local drug delivery could reduce side effects and would be a distinct improvement compared to existing therapeutic approaches, e.g. in the local therapy of Helicobacter...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9834-1
更新日期：2009-05-01 00:00:00
abstract：PURPOSE:The work aims at investigating the correlation of water sorption potential with different measures of molecular mobility in an annealed amorphous model compound (trehalose). METHODS:Amorphous trehalose, prepared by freeze-drying, was annealed at 100°C (17°C < T (g)) for up to 120 h. Global mo...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0910-6
更新日期：2013-03-01 00:00:00
abstract：:A liposomal formulation of methylprednisolone (L-MPL) was developed to improve localization of this immunosuppressant in lymphatic tissues. Liposomes containing MPL were formulated from a mixture of phosphatydylcholine and phosphatydylglycerol (molar ratio, 9:1) and sized by extrusion through a 0.1-micron membrane. Ma...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018954704886
更新日期：1993-10-01 00:00:00
abstract：PURPOSE:This study addresses the effect of freezing and thawing on a therapeutic monoclonal antibody (mAb) solution and the corresponding buffer formulation. Particle formation, crystallization behaviour, morphology changes and cryo-concentration effects were studied after varying the freezing and thawing rates, buffer...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2378-5
更新日期：2018-03-19 00:00:00
abstract：PURPOSE:Basal insulins with improved kinetic properties can potentially be produced using acylation by fatty acids that enable soluble, high-molecular weight complexes to form post-injection. A series of insulins, acylated at B29 with fatty acids via glutamic acid spacers, were examined to deduce the structural require...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0739-z
更新日期：2012-08-01 00:00:00
abstract：:The pharmacokinetics of 2',3'-dideoxyinosine (ddI) were examined in rats given intravenous doses of 8, 40, or 200 mg/kg. The concentrations of ddI in whole blood and plasma were identical. The concentration decline was multiexponential, with mean half-lives of 2 and 20 min for the first and second phases, respectively...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015866714224
更新日期：1992-08-01 00:00:00
abstract：:Under the heading "Methods-Synthesis of the Bioreducible Modified-PAE (mPAE)", on page 3, line 14-17, there is an error. The quantity unit of PAE and 2-iminothiolane hydrochloride needs to be corrected to mg instead of g. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,已发布勘误
doi：10.1007/s11095-018-2488-0
更新日期：2018-09-05 00:00:00
abstract：PURPOSE:To improve the delivery of liposomes to tumors using P-selectin glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are upregulated on tumorassociated endothelium. METHODS:PSGL1 was orientated and presented on the surface of liposomes to achieve optimal selectin binding using a novel st...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0875-5
更新日期：2013-02-01 00:00:00
abstract：PURPOSE:Present study assessed the influence of gallate esterification on the anti-cancer activity of procyanidin B2 (B2) in androgen-dependent human prostate carcinoma LNCaP cells employing B2-3,3'-di-O-gallate (B2-G(2)), two mono-gallate esters B2-3-O-gallate (B2-3G) and B2-3'-O-gallate (B2-3'G) and the parent compou...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-0037-6
更新日期：2010-04-01 00:00:00
abstract：:Primaquine (I), a 6-methoxy-8-aminoqumoline derivative used for the treatment of malaria has previously been shown to be metabolized to 8-(3-carboxy-l-methyl-propylamino)-6-methoxyquinoline by both micro-organisms and laboratory rats. Reported herein is the synthesis of this novel metabolite. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016311616719
更新日期：1984-03-01 00:00:00
abstract：:The fluxes of nitroglycerine (NG) through human abdominal epidermis from different individuals were measured in vitro at 32°C. The mean NG flux for the entire group was 16.9 µg/cm(2) × hr, with a standard deviation of 47.7%. There are no significant differences in the means and the variances of NG fluxes between males...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016381017357
更新日期：1986-02-01 00:00:00
abstract：PURPOSE:To investigate the potential of a novel lipid carrier, comprising beads of alpha-cyclodextrin and soybean oil, for topical drug delivery. Adapalene was chosen as a model drug to explore the ability of the beads to encapsulate and release a highly lipophilic compound. MATERIALS AND METHODS:Adapalene-loaded bead...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9395-0
更新日期：2008-02-01 00:00:00
