Protein adsorption, desorption, and aggregation mediated by solid-liquid interfaces.


:Adsorption of proteins to solid-fluid interfaces is often empirically found to promote formation of soluble aggregates and larger, subvisible, and visible particles, but key stages in this process are often difficult to probe directly. Aggregation mediated by adsorption to water-silicon oxide (SiOx) interfaces, akin to hydrated glass surfaces, was characterized as a function of pH and ionic strength for alpha-chymotrypsinogen (aCgn) and for a monoclonal antibody (IgG1). A flow cell permitted neutron reflectivity for protein layers adsorbed to clean SiOx surfaces, as well as after successive "rinse" steps. Aggregates recovered in solution after gently "rinsing" the surface were characterized by neutron scattering, microscopy, and fluorescence spectroscopy. IgG1 molecules oriented primarily "flat" against the SiOx surface, with the primary protein layer desorbed to a minimal extent, whereas a diffuse overlayer was easily rinsed off. aCgn molecules were resistant to desorption when they appeared to be unfolded at the interface, but were otherwise easily removed. For cases where strong binding occurred, protein that did desorb was a mixture of monomer and small amounts of HMW aggregates (for aCgn) or subvisible particles (for IgG1). Changes in adsorption and/or unfolding with pH indicated that electrostatic interactions were important in all cases.


J Pharm Sci


Perevozchikova T,Nanda H,Nesta DP,Roberts CJ




Has Abstract


2015-06-01 00:00:00














  • Effects of freeze-dry processing conditions on the crystallization of pentamidine isethionate.

    abstract::The results of this study show that pentamidine isethionate (PI) can exist in at least four crystalline forms-three anhydrates designated as forms A, B, and C, and a trihydrate. Form C is the high-temperature modification, produced by heating forms A, B, and the trihydrate above 130 degrees C and cannot be produced un...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Chongprasert S,Griesser UJ,Bottorff AT,Williams NA,Byrn SR,Nail SL

    更新日期:1998-09-01 00:00:00

  • Automated potentiometric procedure for studying dissolution kinetics acidic drugs under sink conditions.

    abstract::An automated potentiometric procedure was used for studying in vitro dissolution kinetics of acidic drugs. Theoretical considerations indicated that the pH-stat method could be used to establish approximate sink conditions or, possibly, a perfect sink. Data obtained from dissolution studies using the pH-stat method we...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Underwood FL,Cadwallader DE

    更新日期:1978-08-01 00:00:00

  • Analytical methods for the determination of sulindac and metabolites in plasma, urine, bile, and gastric fluid by liquid chromatography using ultraviolet detection.

    abstract::A high-performance liquid chromatographic method using a linear elution gradient has been developed for the analysis of sulindac, sulindac sulfone, and sulindac sulfide in plasma, urine, bile, and gastric fluid. The methodology uses reverse-phase, radial compression chromatography with gradient elution, and UV detecti...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Musson DG,Vincek WC,Constanzer ML,Detty TE

    更新日期:1984-09-01 00:00:00

  • Interlaboratory comparison of analytical methods for residual ethylene oxide at low concentration levels in medical device materials.

    abstract::An interlaboratory comparison of two extraction methods and one thermal desorption test method for the quantification of ethylene oxide (EO) by gas chromatography in two common medical device materials, high density polyethylene (HDPE) and plasticized polyvinyl chloride (PVC), was conducted by 15 laboratories. The thr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Lao NT,Lu HT,Rego A,Kosakowski RH,Burgess DJ,Hume RD

    更新日期:1995-05-01 00:00:00

  • Chemical modification of hyaluronic acid for intraoral application.

    abstract::This study was aimed to investigate chemical preactivated thiomers for their potential use in mucosal drug delivery. Thiomers--thiolated polymers--are mucoadhesive polymers with sulfhydryl group-bearing side chains. Thiomers are synthesized by covalent attachment of low molecular mass compounds bearing sulfhydryl grou...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Laffleur F,Röggla J,Idrees MA,Griessinger J

    更新日期:2014-08-01 00:00:00

  • Pharmacokinetic properties of a novel gastric proton pump inhibitor, (+/-)-2-[(4-methoxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9- yl)sulfinyl]-1H-benzimidazole sodium salt, in healthy subjects.

    abstract::The pharmacokinetics and safety of TY-11345 [(+/-)-2-[(4-methoxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9- yl)sulfinyl]-1H-benzimidazole sodium salt], a novel gastric proton pump inhibitor, were studied in healthy male volunteers after single (20, 40, and 80 mg) and repeated oral doses (60 mg, once daily for 7 day...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 临床试验,杂志文章


    authors: Uematsu T,Nakano M,Kosuge K,Nagai A,Sato A,Nakashima M

    更新日期:1994-10-01 00:00:00

  • Isomerization of ceftibuten in aqueous solution.

    abstract::The isomerization reactions of ceftibuten and ceftibuten-related compounds in aqueous solution were investigated to estimate the substitution effect on the isomerization reaction and identify the three proximal dissociation constants of ceftibuten kinetically from the pH-rate profiles. The isomerization reaction of ce...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Hashimoto N,Hirano K

    更新日期:1998-09-01 00:00:00

  • Effect of absorbents on water vapor transmission of free and applied polymer films.

    abstract::The influence of different types of absorbents on moisture transmission through free (cast films) and applied (coated tablets) polymer films was investigated. In free film studies, lubricated granulations were considered to be the absorbent. The compressed tablet was considered to be the absorbent in applied film stud...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Amann AH

    更新日期:1976-04-01 00:00:00

  • Simultaneous detection and analysis of protein aggregation and protein unfolding by size exclusion chromatography with post column addition of the fluorescent dye BisANS.

    abstract::For development and optimization of protein formulation sensitive analytical tools are required to follow both aggregation and changes in protein structure. The latter can be seen as the beginning of physical instability leading to aggregation. The focus of this work laid on the development of a novel analysis simulta...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Printz M,Friess W

    更新日期:2012-02-01 00:00:00

  • Specific interactions in high concentration antibody solutions resulting in high viscosity.

    abstract::The purpose of this work was to investigate the self-associating behavior observed in high concentration monoclonal antibody (MAb1) solutions at pH 6.0. Zeta potential measurements over the pH range (4.0-9.0) showed lower net charges present on the molecule at pH 6.0 and 7.0. The point of zero charge or crossover from...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Yadav S,Liu J,Shire SJ,Kalonia DS

    更新日期:2010-03-01 00:00:00

  • Stability of the Hsp90 inhibitor 17AAG hydroquinone and prevention of metal-catalyzed oxidation.

    abstract::17-(allylamino)-17-demethoxygeldanamycin (17AAG) is a benzoquinone ansamycin Hsp90 inhibitor which has promising anticancer activity in vitro, in animal models and in clinical trials. 17AAG has poor water-solubility which is a potential problem for clinical formulation. The hydroquinone derivative of 17AAG, 17AAG hydr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Guo W,Siegel D,Ross D

    更新日期:2008-12-01 00:00:00

  • Physicochemical characterization of nedocromil bivalent metal salt hydrates. 3. Nedocromil calcium.

    abstract::A crystalline pentahydrate and a crystalline 8/3 hydrate of nedocromil calcium (NC) were prepared. The relationships between these solid phases and the nature of the water interactions in their structures were studied through characterization by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA)...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Zhu H,Halfen JA,Young VG Jr,Padden BE,Munson EJ,Menon V,Grant DJ

    更新日期:1997-12-01 00:00:00

  • Crystal structures of azathioprine dihydrate and 6-methylmercaptopurine trihydrate.

    abstract::The crystal and molecular structures of 6-methylmercaptopurine trihydrate and of azathioprine dihydrate were determined by the use of three-dimensional, X-ray, diffractometer data and were refined by least squares. Both molecules crystallize in the N(9)-H tautomer form, in contrast to the N(7)-H tautomer form found in...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Cook WJ,Bugg CE

    更新日期:1975-02-01 00:00:00

  • Effect of bile salts on nasal permeability in vitro.

    abstract::Nasal mucosa excised from dogs or rabbits was mounted as a flat sheet in an in vitro chamber. The permeability was assessed by measuring the unidirectional flux of the radiolabeled tracer compounds, water, sucrose, polyethylene glycol, and cholecystokinin octapeptide. The permeability coefficients calculated from the ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Hersey SJ,Jackson RT

    更新日期:1987-12-01 00:00:00

  • Evaluation of New Chemical Entities as Substrates of Liver Transporters in the Pharmaceutical Industry: Response to Regulatory Requirements and Future Steps.

    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


    authors: Okudaira N

    更新日期:2017-09-01 00:00:00

  • Solid-state dispersions employing urethan.

    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


    authors: Maulding HV

    更新日期:1978-03-01 00:00:00

  • Controlled and complete release of a model poorly water-soluble drug, prednisolone, from hydroxypropyl methylcellulose matrix tablets using (SBE)(7m)-beta-cyclodextrin as a solubilizing agent.

    abstract::Sustained-release formulations such as hydroxypropyl methylcellulose (HPMC)-based hydrophilic matrix tablets of poorly water-soluble drugs often result in incomplete release because of the poor solubility and dissolution rate of the drug in the hydrophilic matrix. Sulfobutylether-beta-cyclodextrins ((SBE)(7M)-beta-CDs...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Rao VM,Haslam JL,Stella VJ

    更新日期:2001-07-01 00:00:00

  • Per Artursson's Major Contributions to the Caco-2 Cell Literature in Pharmaceutical Sciences.

    abstract::This edition of the Journal of Pharmaceutical Sciences is dedicated to the wonderful career of Per Artursson from the Uppsala University. My Commentary focusses on Per's major contributions to the Caco-2 cell literature over the past 30 years. Two especially influential papers have been cited more than 1000 times out ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Brayden DJ

    更新日期:2021-01-01 00:00:00

  • Hepatobiliary disposition of liposomal amphotericin B in the isolated perfused rat liver.

    abstract::The hepatic distribution, biliary excretion, and mass balance of liposomal amphotericin B (L-AmB) were investigated in recirculated isolated perfused rat liver. The results were compared with those from the conventional AmB formulation, amphotericin B deoxycholate (D-AmB). L-AmB was introduced as a bolus into the perf...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Hong Y,Ramzan I,McLachlan AJ

    更新日期:2005-01-01 00:00:00

  • The Role of Physiologically Based Oral Absorption Modelling in Formulation Development Under a Quality by Design Paradigm.

    abstract::Within the last decade, Quality by Design (QbD) has been getting increased attention in its implementation in the development of pharmaceutical drug products. Understanding of the impact of formulation composition and process on clinical performance is a centerpiece of QbD. Physiologically based pharmacokinetic modeli...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Kesisoglou F

    更新日期:2017-04-01 00:00:00

  • A general approach for the prediction of the intestinal absorption of drugs: regression analysis using the physicochemical properties and drug-membrane electrostatic interaction.

    abstract::A general method for predicting the intestinal absorption of a wide range of drugs using multiple regression analysis of their physicochemical properties and the drug-membrane electrostatic interaction was developed. The absorption rates of tested drugs from rat jejunum were measured by the in situ single-pass perfusi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Sugawara M,Takekuma Y,Yamada H,Kobayashi M,Iseki K,Miyazaki K

    更新日期:1998-08-01 00:00:00

  • Effects of phenobarbital on the distribution pharmacokinetics and biological half-lives of model nonmicrosomal enzyme metabolizable sulfonamides in rats.

    abstract::The pharmacokinetics of sulfisoxazole and sulfanilamide were studied in control rats and in rats treated for 5 days with a daily 100 mg/kg ip dose of phenobarbital. These drugs represent the organic anionic and nonionized drugs, respectively, whose nonmicrosomal enzymatic metabolisms were unstimulated by phenobarbital...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Nagwekar JB,Kundu S

    更新日期:1982-04-01 00:00:00

  • Synthesis and evaluation of 3-halocyclophosphamides and analogous compounds as novel anticancer "pro-prodrugs".

    abstract::3-Fluoro-, 3-chloro-, and 3-bromocyclophosphamide were prepared from the reaction of trifluoromethylhypofluorite, sodium hypochlorite, and bromine with the anticancer drug cyclophosphamide. Treatment of cis- and trans-4-phenylcyclophosphamide and 5,6-benzocyclophosphamide with sodium hypochlorite afforded cis- and tra...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Zon G,Ludeman SM,Ozkan G,Chandrasegaran S,Hammer CF,Dickerson R,Mizuta K,Egan W

    更新日期:1983-06-01 00:00:00

  • Thai Silk Fibroin/Gelatin Sponges for the Dual Controlled Release of Curcumin and Docosahexaenoic Acid for Anticancer Treatment.

    abstract::In this study, curcumin and/or docosahexaenoic acid (DHA) were encapsulated in Thai silk fibroin/gelatin (SF/G) sponges, prepared at different blending ratios, aimed to be applied as a controlled release system for localized cancer therapy. The SF/G sponges were fabricated by freeze-drying and glutaraldehyde cross-lin...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Lerdchai K,Kitsongsermthon J,Ratanavaraporn J,Kanokpanont S,Damrongsakkul S

    更新日期:2016-01-01 00:00:00

  • Correlation of absorption of sulfamethazine boluses with dissolution using a new dissolution apparatus for veterinary tablets.

    abstract::A rotating-basket apparatus for dissolution testing of veterinary bolus tablets was designed and constructed. Sulfamethazine boluses containing different disintegrating agents were evaluated in vitro and by blood level data following administration to cattle. The dissolution t50 and various pharmacokinetic parameters ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Frazier WF,Nuessle NO

    更新日期:1976-12-01 00:00:00

  • Nasal absorption of natural contraceptive steroids in rats-progesterone absorption.

    abstract::Contraceptive natural steroids, such as progesterone and estradiol, are ineffective when administered orally because of extensive metabolism in the gastrointestinal (GI) tract during absorption and first-pass metabolism. Consequently, highly potent and potentially harmful synthetic steroids are now being used in oral...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Hussain AA,Hirai S,Bawarshi R

    更新日期:1981-04-01 00:00:00

  • Rapid throughput solubility screening method for BCS class II drugs in animal GI fluids and simulated human GI fluids using a 96-well format.

    abstract::A rapid solubility-screening assay was developed with a focus on Biopharmaceutic Classification Scheme (BCS) class II drug solubility in animal and simulated human gastrointestinal (GI) fluids. The assay enables biologically promising drug leads to be evaluated for solubility limitations earlier in the drug developmen...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Guo J,Elzinga PA,Hageman MJ,Herron JN

    更新日期:2008-04-01 00:00:00

  • Physicochemical properties of A-75998, an antagonist of luteinizing hormone releasing hormone.

    abstract::The physicochemical properties of A-75998, a synthetic antagonist of luteinizing hormone releasing hormone with potential for treatment of hormone-sensitive cancers and endometriosis, are described. An accelerated solution stability study indicated that the compound is relatively stable and showed a U-shaped pH-rate p...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Cannon JB,Krill SL,Porter WR

    更新日期:1995-08-01 00:00:00

  • Fluorometric determination of trifluoromethyl-substituted 2,3-bis(4-methoxyphenyl)indoles in biological materials.

    abstract::Interest in the 5-, 6-, and 7-trifluoromethyl-substituted 2,3-bis(4-methoxyphenyl)indoles as potent, orally active anti-inflammatory agents required a method for their determination in serum, urine, and feces to permit studies of their absorption, metabolism, and excretion. A simple, rapid, sensitive, and specific pro...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Kaiser DG,Liggett WF,Forist AA

    更新日期:1976-12-01 00:00:00

  • Investigation of the Changes in Aerosolization Behavior Between the Jet-Milled and Spray-Dried Colistin Powders Through Surface Energy Characterization.

    abstract::This study aimed to investigate the surface energy factors behind improved aerosolization performance of spray-dried colistin powder formulations compared with those produced by jet milling. Inhalable colistin powder formulations were produced by jet milling or spray drying (with or without l-leucine). Scanning electr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Jong T,Li J,Morton DA,Zhou QT,Larson I

    更新日期:2016-03-01 00:00:00