In vivo fluorescence imaging of IgG1 aggregates after subcutaneous and intravenous injection in mice.


PURPOSE:To monitor the biodistribution of IgG1 aggregates upon subcutaneous (SC) and intravenous (IV) administration in mice and measure their propensity to stimulate an early immune response. METHODS:A human mAb (IgG1) was fluorescently labeled, aggregated by agitation stress and injected in SKH1 mice through SC and IV routes. The biodistribution of monomeric and aggregated formulations was monitored over 47 days by fluorescence imaging and the early immune response was measured by quantifying the level of relevant cytokines in serum using a Bio-plex assay. RESULTS:The aggregates remained at the SC injection site for a longer time than monomers but after entry into the systemic circulation disappeared faster than monomers. Upon IV administration, both monomers and aggregates spread rapidly throughout the circulation, and a strong accumulation in the liver was observed for both species. Subsequent removal from the circulation was faster for aggregates than monomers. No accumulation in lymph nodes was observed after SC or IV administration. Administration of monomers and aggregates induced similar cytokine levels, but SC injection resulted in higher cytokine levels than IV administration. CONCLUSION:These results show differences in biodistribution and residence time between IgG1 aggregates and monomers. The long residence time of aggregates at the SC injection site, in conjunction with elevated cytokine levels, may contribute to an enhanced immunogenicity risk of SC injected aggregates compared to that of monomers.


Pharm Res


Pharmaceutical research


Filipe V,Que I,Carpenter JF,Löwik C,Jiskoot W




Has Abstract


2014-01-01 00:00:00












  • Swelling and dissolution kinetics during peptide release from erodible anionic gel beads.

    abstract::The transient dynamic swelling and dissolution behavior during the release of a growth hormone releasing peptide, [D-Trp2-D-Phe5]GHRP, from erodible, non-cross-linked poly(methyl methacrylate-co-methacrylic acid) (PMMA/MAA) beads has been investigated at pH 7.4 as a function of buffer concentration. Although the swell...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Lee PI

    更新日期:1993-07-01 00:00:00

  • Phagocytosis and phagosomal fate of surface-modified microparticles in dendritic cells and macrophages.

    abstract:PURPOSE:We compared cationic, polyamine-coated microparticles (MPs) and anionic, protein-coated MPs with respect to their phagocytosis and phagosomal fate in dendritic cells (DCs) and macrophages (Mphi). METHODS:Polystyrene MPs were surface modified by covalent coupling with fluorescein isothiocyanate-labeled polyamin...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Thiele L,Merkle HP,Walter E

    更新日期:2003-02-01 00:00:00

  • Optimizing the Entrainment Geometry of a Dry Powder Inhaler: Methodology and Preliminary Results.

    abstract:PURPOSE:For passive dry powder inhalers (DPIs) entrainment and emission of the aerosolized drug dose depends strongly on device geometry and the patient's inhalation manoeuvre. We propose a computational method for optimizing the entrainment part of a DPI. The approach assumes that the pulmonary delivery location of ae...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Kopsch T,Murnane D,Symons D

    更新日期:2016-11-01 00:00:00

  • Pharmacokinetic study of an iridoid glucoside: aucubin.

    abstract::Aucubin, a promising hepatoprotecting iridoid glucoside, was given intravenously (iv), orally (po), intraperitoneally (ip), and hepatoportally (pv) to rats. A linear pharmacokinetic behavior was obtained after iv administation of 400-400 mg/kg of aucubin. The half-life of aucubin in the postdistributive phase (t1/2, b...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Suh NJ,Shim CK,Lee MH,Kim SK,Chang IM

    更新日期:1991-08-01 00:00:00

  • Comparison of CYP2D6 content and metoprolol oxidation between microsomes isolated from human livers and small intestines.

    abstract:PURPOSE:To assess the role of intestinal CYP2D6 in oral first-pass drug clearance by comparing the enzyme content and catalytic activity of a prototype CYP2D6 substrate, metoprolol, between microsomes prepared from human intestinal mucosa and from human livers. METHODS:Microsomes were prepared from a panel of 31 human...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Madani S,Paine MF,Lewis L,Thummel KE,Shen DD

    更新日期:1999-08-01 00:00:00

  • Fatty acid-RGD peptide amphiphile micelles as potential paclitaxel delivery carriers to α(v)β₃ integrin overexpressing tumors.

    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


    authors: Javali NM,Raj A,Saraf P,Li X,Jasti B

    更新日期:2012-12-01 00:00:00

  • Controlled delivery systems for proteins using polyanhydride microspheres.

    abstract::A method to provide near-constant sustained release of high molecular weight, water-soluble proteins from polyanhydride microspheres is described. The polyanhydrides used were poly(fatty acid dimer) (PFAD), poly(sebacic acid) (PSA), and their copolymers [P(FAD-SA)]. P(FAD-SA) microspheres containing proteins of differ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Tabata Y,Gutta S,Langer R

    更新日期:1993-04-01 00:00:00

  • In vivo effects of glycyl-glutamate and glycyl-sarcosine on gabapentin oral absorption in rat.

    abstract:PURPOSE:The objective of this study was to evaluate the in vivo consequences of glycyl-glutamate coadministration on gabapentin oral absorption. METHODS:Rats were administered gabapentin (10 mg/kg plus radiotracer) by gastric gavage, in the absence and presence of dipeptides, and by intravenous administration. Serial ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Nguyen TV,Fleisher D,Smith DE

    更新日期:2007-08-01 00:00:00

  • Site specific rectal drug administration in man with an osmotic system: influence on "first-pass" elimination of lidocaine.

    abstract::Lidocaine was administered to healthy volunteers at different sites in the rectum. Unchanged drug and monoethylglycinexylidide (MEGX) concentrations were measured in plasma with a newly developed gas chromatographic method. Lidocaine was given rectally by means of an osmotic system (Osmet(®)) which delivered 25 mg/h a...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: de Leede LG,de Boer AG,Feijen CD,Breimer DD

    更新日期:1984-05-01 00:00:00

  • Microbial and mammalian metabolism studies of the semisynthetic antimalarial, anhydrodihydroartemisinin.

    abstract::Microbial metabolism studies of the semisynthetic antimalarial anhydrodihydroartemisinin (1), have shown that it is metabolized by a number of microorganisms. Large scale fermentation with Streptomyces lavendulae L-105 and Rhizopogon species (ATCC 36060) have resulted in the isolation of four microbial metabolites. Th...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Khalifa SI,Baker JK,Rogers RD,el-Feraly FS,Hufford CD

    更新日期:1994-07-01 00:00:00

  • The mean dissolution time depends on the dose/solubility ratio.

    abstract:PURPOSE:To investigate the relationship between mean dissolution time (MDT) and dose/solubility ratio (q) using the diffusion layer model. METHODS:Using the classic Noyes-Whitney equation and considering a finite dose, we derived an expression for MDT as a function of q under various conditions. q was expressed as a d...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Rinaki E,Dokoumetzidis A,Macheras P

    更新日期:2003-03-01 00:00:00

  • Pharmacokinetics of once-a-month injectable microspheres of leuprolide acetate.

    abstract::The pharmacokinetic parameters of leuprolide acetate, a potent analogue of LH-RH, were determined in rats and dogs after i.v. and s.c. dosing with leuprolide solution. The effective human dose of once-a-month injectable microspheres of leuprolide was estimated to be about 3.2 to 8.1 mg analogue/month using these param...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Okada H,Inoue Y,Heya T,Ueno H,Ogawa Y,Toguchi H

    更新日期:1991-06-01 00:00:00

  • Improved inhalation behavior of steroid KSR-592 in vitro with Jethaler by polymorphic transformation to needle-like crystals (beta-form).

    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


    authors: Ikegami K,Kawashima Y,Takeuchi H,Yamamoto H,Isshiki N,Momose D,Ouchi K

    更新日期:2002-10-01 00:00:00

  • Photokinetic Drug Delivery: Near infrared (NIR) Induced Permeation Enhancement of Bevacizumab, Ranibizumab and Aflibercept through Human Sclera.

    abstract:PURPOSE:Permeation studies, with near infrared (NIR) light and anti-aggregation antibody formulation, were used to investigate the in vitro permeation of bevacizumab, ranibizumab and aflibercept through human sclera. METHODS:A vertical, spherical Franz cell diffusion apparatus was used for this scleral tissue permeati...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Giannos SA,Kraft ER,Zhao ZY,Merkley KH,Cai J

    更新日期:2018-03-29 00:00:00

  • Synthetic glycopeptide-based delivery systems for systemic gene targeting to hepatocytes.

    abstract:PURPOSE:To design, synthesize, and test synthetic glycopeptide-based delivery systems for gene targeting to hepatocytes by systemic administration. METHODS:All peptides were synthesized by the solid phase method developed using Fmoc chemistry on a peptide synthesizer. The binding of galactosylated peptides to HepG2 ce...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Anwer K,Logan M,Tagliaferri F,Wadhwa M,Monera O,Tung CH,Chen W,Leonard P,French M,Proctor B,Wilson E,Singhal A,Rolland A

    更新日期:2000-04-01 00:00:00

  • Prodrugs of peptides. 11. Chemical and enzymatic hydrolysis kinetics of N-acyloxymethyl derivatives of a peptide-like bond.

    abstract::Various carboxylic acid esters of the N-hydroxymethyl derivative of N-benzyloxycarbonylglycine benzylamide, used as a peptide-like model, were prepared and their decomposition kinetics studied in aqueous solution and in human plasma solutions. These N-acyloxymethylamide derivatives were found to undergo a facile decom...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Bundgaard H,Rasmussen GJ

    更新日期:1991-10-01 00:00:00

  • Comparison of the hanson microette and the Van Kel apparatus for in vitro release testing of topical semisolid formulations.

    abstract:PURPOSE:The major goal of this study was to compare the relative utility of the Hanson Microette and the Van Kel apparatus, two fully automated devices, as in vitro release tests (IVRT) for semisolids. We attempted to develop methodology that can be used to discriminate formulation changes, and to evaluate the precisio...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Rapedius M,Blanchard J

    更新日期:2001-10-01 00:00:00

  • On technological and immunological benefits of multivalent single-injection microsphere vaccines.

    abstract:PURPOSE:With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity. METHODS:Mono- and multi...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Boehm G,Peyre M,Sesardic D,Huskisson RJ,Mawas F,Douglas A,Xing D,Merkle HP,Gander B,Johansen P

    更新日期:2002-09-01 00:00:00

  • Dissolution techniques for in vitro testing of dry powders for inhalation.

    abstract:PURPOSE:To evaluate different dissolution testing methods and subsequently develop a simple to perform but reproducible and discriminating dissolution technique for inhalative powders. METHODS:From a dry powder a fraction of aerosolized particles with an aerodynamic particle size below 5 μm was collected on regenerate...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: May S,Jensen B,Wolkenhauer M,Schneider M,Lehr CM

    更新日期:2012-08-01 00:00:00

  • Temperature-Induced Surface Effects on Drug Nanosuspensions.

    abstract:PURPOSE:The trial-and-error approach is still predominantly used in pharmaceutical development of nanosuspensions. Physicochemical dispersion stability is a primary focus and therefore, various analytical bulk methods are commonly employed. Clearly less attention is directed to surface changes of nanoparticles even tho...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Aleandri S,Schönenberger M,Niederquell A,Kuentz M

    更新日期:2018-02-21 00:00:00

  • Nebulization of liposomes. II. The effects of size and modeling of solute release profiles.

    abstract::A series of carboxyfluorescein (CF)-containing multilamellar vesicle (MLV) dispersions was prepared and extruded through polycarbonate membranes ranging in size from 0.2 to 5 microns. Vesicle dispersions were nebulized for 80 min using a Collison nebulizer, and the release of CF was monitored during nebulization. Solu...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Niven RW,Speer M,Schreier H

    更新日期:1991-02-01 00:00:00

  • Enhanced delivery of 5-iodo-2'-deoxyuridine to the brain parenchyma.

    abstract::5'-Ester derivatives of 5-iodo-2'-deoxyuridine (IDU) with varying degrees of lipophilicity were examined to evaluate the effectiveness of lipophilic ester prodrugs for enhanced and sustained delivery of IDU to the brain parenchyma. Approximately 1.0% (1.0 +/- 0.19; n = 4) of the total radioactivity was found in the br...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Ghosh MK,Mitra AK

    更新日期:1992-09-01 00:00:00

  • Contribution of lysosomes to the subcellular distribution of basic drugs in the rat liver.

    abstract:PURPOSE:We examined the subcellular distribution of the basic drugs, chlorpromazine (CPZ), imipramine (IMP) and biperiden (BP), in rat liver, and evaluated the contribution of lysosome (Lys) to their intracellular distribution in comparison with that of mitochondria (Mit). METHODS:In an in vivo distribution, the conce...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Ishizaki J,Yokogawa K,Hirano M,Nakashima E,Sai Y,Ohkuma S,Ohshima T,Ichimura F

    更新日期:1996-06-01 00:00:00

  • Physicochemical properties of liposomes affecting apoptosis induced by cationic liposomes in macrophages.

    abstract:PURPOSE:Cationic liposomes are expected to be useful as nonviral vectors for gene delivery. Cationic liposomes showed cytotoxicity, and we proposed that the cytotoxicity is through apoptosis. In this study, we examined the effects of liposomal properties, such as liposomal charge, size, membrane fluidity, and PEG coati...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Takano S,Aramaki Y,Tsuchiya S

    更新日期:2003-07-01 00:00:00

  • The use of disaccharides in inhibiting enzymatic activity loss and secondary structure changes in freeze-dried β-galactosidase during storage.

    abstract:PURPOSE:The purpose of this study is to show how disaccharides differ in their ability to protect lyophilized β-galactosidase from enzymatic activity loss and secondary structure changes during storage. METHODS:β-galactosidase was lyophilized with trehalose, sucrose, cellobiose or melibiose at 2:1, 20:1 and 40:1 excip...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Heljo VP,Jouppila K,Hatanpää T,Juppo AM

    更新日期:2011-03-01 00:00:00

  • Pharmaceutical evaluation of gas-filled microparticles as gene delivery system.

    abstract:PURPOSE:To produce and characterize a nonviral ultrasound-controlled release system of plasmid DNA (pDNA) encapsulated in gas-filled poly(D,L-lactide-co-glycolide) microparticles (PLGA-MPs). METHODS:Different cationic polymers were used to form pDNA/polymer complexes to enhance the stability of pDNA during micropartic...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Seemann S,Hauff P,Schultze-Mosgau M,Lehmann C,Reszka R

    更新日期:2002-03-01 00:00:00

  • Mechanistic studies on effervescent-induced permeability enhancement.

    abstract:PURPOSE:To determine the mechanism(s) by which effervescence induces penetration enhancement of a broad range of compounds ranging in size, structure, and other physiocochemical properties across rat and rabbit small intestinal epithelium. METHODS:Effervescent induced penetration enhancement was investigated in vitro ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Eichman JD,Robinson JR

    更新日期:1998-06-01 00:00:00

  • Formulation and physical characterization of large porous particles for inhalation.

    abstract:PURPOSE:Relatively large (>5 microm) and porous (mass density <0.4 g/cm3) particles present advantages for the delivery of drugs to the lungs, e.g., excellent aerosolization properties. The aim of this study was, first, to formulate such particles with excipients that are either FDA-approved for inhalation or endogenou...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Vanbever R,Mintzes JD,Wang J,Nice J,Chen D,Batycky R,Langer R,Edwards DA

    更新日期:1999-11-01 00:00:00

  • Pharmaceutical properties of loracarbef: the remarkable solution stability of an oral 1-carba-1-dethiacephalosporin antibiotic.

    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


    authors: Pasini CE,Indelicato JM

    更新日期:1992-02-01 00:00:00

  • Origin of the isoelectric heterogeneity of monoclonal immunoglobulin h1B4.

    abstract::The origin of the microheterogeneity of a highly purified antiinflammatory humanized monoclonal antibody prepared in mammalian cell culture has been investigated. This antibody is an IgG directed toward human CD18 (a subunit of leukocyte integrins). When the IgG preparation is subjected to isoelectric focusing, it is ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Tsai PK,Bruner MW,Irwin JI,Ip CC,Oliver CN,Nelson RW,Volkin DB,Middaugh CR

    更新日期:1993-11-01 00:00:00