Optimal PEGylation can improve the exposure of interferon in the lungs following pulmonary administration.


:The utility of inhaled protein therapeutics to treat lung-resident diseases is limited by protein degradation in the lungs and rapid clearance. This study therefore aimed to evaluate the impact of PEGylation on the lung and systemic exposure of interferon (IFN) α2 after intratracheal administration to rats. An inverse correlation was observed between PEG chain length and systemic exposure, where bioavailability was 5.5% for the 31 kDa PEGylated construct and <0.4% for the 60 kDa PEGylated construct when compared with 15% for native IFN (19 kDa). Retention of PEGylated IFNα within the lungs increased 2.5-fold to threefold when compared with native IFN. When comparing the lung and systemic exposure of PEGylated and native IFN in terms of protein biological activity, the 31 kDa PEGylated construct increased exposure by 50% and 100%, respectively, when compared with native IFN, but the 60 kDa PEG construct offered no benefit. Preliminary work also indicated that the conjugation of IFNγ with 10 kDa PEG significantly increases the retention of the protein within the lung. Optimal PEGylation may therefore be used as a means to improve the exposure of lung-resident diseases to therapeutic cytokines and potentially reduce systemic exposure and side effects as well as dosing frequency.


J Pharm Sci


Mcleod VM,Chan LJ,Ryan GM,Porter CJ,Kaminskas LM




Has Abstract


2015-04-01 00:00:00














  • An examination of the thermodynamics of fusion, vaporization, and sublimation of (R,S)- and (R)-flurbiprofen by correlation gas chromatography.

    abstract::The vaporization, fusion, and sublimation enthalpies of (R,S)- and (R)-flurbiprofen at T = 298.15 K are reported and compared with literature values when available. Correlation gas chromatography experiments were first performed to identify appropriate standards that could be used for materials containing a single flu...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Umnahanant P,Hasty D,Chickos J

    更新日期:2012-06-01 00:00:00

  • An evaluation of the antibacterial activities of combinations of sulfonamides, trimethoprim, dibromopropamidine, and silver nitrate compared with their uptakes by selected bacteria.

    abstract::Modifications of antibacterial activity have been demonstrated using combinations of two antibacterials from trimethoprim, sulfonamides (sulfadiazine, sulfamerazine, and silver sulfadiazine), silver nitrate, and dibromopropamidine isethionate, either formulated in a cream base or dissolved in peptone water. The creams...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Richards RM,Taylor RB,Xing DK

    更新日期:1991-09-01 00:00:00

  • Determination of a quaternary mixture of vitamins B6, B1, and B12 and uridine 5'-triphosphate, by derivative spectrophotometry.

    abstract::A new method for determining a quaternary mixture of vitamins B6, B1, and B12 and uridine 5'-triphosphate (UPT) using second-derivative spectrophotometry is described. Calibration graphs were linear up to 30 micrograms/mL of vitamin B6 at 307 nm (r = 0.9999) and vitamin B1 at 282.7 nm (r = 0.9997) and up to 35 microgr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Morelli B

    更新日期:1995-01-01 00:00:00

  • Heterogeneous nucleation-controlled particulate formation of recombinant human platelet-activating factor acetylhydrolase in pharmaceutical formulation.

    abstract::Clinical lots of recombinant human platelet-activating factor acetylhydrolase (rhPAF-AH) were prepared in a lyophilized formulation. After reconstitution with sterile water for injection to form an aqueous solution (10 mM sodium citrate, 7.5 w/v% sucrose, and 0.1 w/v% Pluronic-F68, pH 6.5), a few visible, slowly growi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Chi EY,Weickmann J,Carpenter JF,Manning MC,Randolph TW

    更新日期:2005-02-01 00:00:00

  • Characterization of a Stable 2,2'-Azobis(2-Methylpropanenitrile) Degradant and Its Use to Monitor the Oxidative Environment During Forced Degradation Studies by Liquid Chromatography/Mass Spectrometry.

    abstract::Azo compounds are commonly used to study radical-mediated degradation of pharmaceutical compounds. The favorable chemical and physical properties of 2,2'-azobis(2-methylpropanenitrile) (AIBN) have made it one of the most widely used compound for these type of studies. This article describes the characterization of a s...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Wells-Knecht KJ,Dunn D

    更新日期:2019-09-01 00:00:00

  • Freezing of Biologicals Revisited: Scale, Stability, Excipients, and Degradation Stresses.

    abstract::Although many biotech products are successfully stored in the frozen state, there are cases of degradation of biologicals during freeze storage. These examples are discussed in the Perspective to emphasize the fact that stability of frozen biologicals should not be taken for granted. Frozen-state degradation (predomin...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审


    authors: Authelin JR,Rodrigues MA,Tchessalov S,Singh SK,McCoy T,Wang S,Shalaev E

    更新日期:2020-01-01 00:00:00

  • Effects of organic anions on the uptake of 1-anilino-8-naphthalenesulfonate by isolated liver cells.

    abstract::Uptake of the fluorescent probe, 1-anilino-8-naphthalene-sulfonate (I) into isolated rat liver cells was studied using both fluorescence and filtration methods. The time course of the fluorescence enhancement of I after addition to the isolated liver cells was analyzed in terms of rapid, medium, and slow phases. The s...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Sugiyama Y,Kimura S,Lin JH,Izukura M,Awazu S,Hanano M

    更新日期:1983-08-01 00:00:00

  • Polynitro aromatic compounds in analytical chemistry II: Reaction of menadione with 2,4-dinitrophenylhydrazine.

    abstract::The intense blue color formed in the official assay of menadione injection by treatment of the sample with 2,4-dinitrophenylhydrazine and ammonia is shown by data from visible light spectra and mass spectra and by comparison of the pKa value with that of the corresponding reaction product of acetone to be due to proto...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Burns LB,Stedman RJ,Tuckerman MM

    更新日期:1978-02-01 00:00:00

  • Pulmonary accumulation of neutral diamine dithiol complexes of technetium-99m.

    abstract::Twenty-two neutral, lipid-soluble 99mTc complexes have been synthesized from diamine dithiol (DADT) ligands which vary in alkyl substitution pattern on nitrogen and carbon. The logarithm of the partition coefficients (log PC), as well as the capacity factor k', of the purified complexes increased linearly with molecul...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Lever SZ,Sun SY,Scheffel UA,Kaltovich FA,Baidoo KE,Goldfarb H,Wagner HN Jr

    更新日期:1994-06-01 00:00:00

  • Cytotoxic effects of methionine alkyl esters and amides in normal and neoplastic cell lines.

    abstract::Homologous series of L-methionine alkyl ester hydrochlorides and tosylates were synthesized and evaluated for in vitro growth inhibitory activity in Meth A sarcoma. Cytotoxicity, as determined by [3H]thymidine incorporation, was found to be directly proportional to alkyl chain length and surface tension lowering activ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Clement MA,Chapman JM,Roberts J

    更新日期:1989-06-01 00:00:00

  • Role of benzyl alcohol in the unfolding and aggregation of interferon α-2a.

    abstract::Benzyl alcohol (BA) is the most widely used antimicrobial preservative in multidose protein formulations, and has been shown to cause protein aggregation. Our previous work on a model protein cytochrome c demonstrated that this phenomenon occurs via partial unfolding. Here, we examine the validity of these results by ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Bis RL,Singh SM,Cabello-Villegas J,Mallela KM

    更新日期:2015-02-01 00:00:00

  • Characterization of native and drug-loaded human low density lipoproteins.

    abstract::Low-density lipoproteins (LDLs), the physiological vehicles for lipids, are potentially useful drug delivery devices for (hydrophobic) drugs. The physicochemical characteristics of LDL loaded with the adriamycin derivative AD 32 or the N-mustard derivative WB 4291 were compared to that of native and reconstituted LDL ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Westesen K,Gerke A,Koch MH

    更新日期:1995-02-01 00:00:00

  • A novel method for determination of drug solubility in polymeric matrices.

    abstract::Crystallization of drugs in metastable, supersaturated adhesive polymeric matrices in transdermal drug delivery devices can be avoided by determination of the solubility of the drug in the adhesive polymer. A novel method is described to determine the solubility of the drug in polymeric matrices. Unlike existing metho...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Jasti BR,Berner B,Zhou SL,Li X

    更新日期:2004-08-01 00:00:00

  • Utilization of Zwitterion-based solutions to dissect the relative effects of solution pH and ionic strength on the aggregation behavior and conformational stability of a fusion protein.

    abstract::Solution pH and ionic strength (I) have complex effects on protein stability. We developed an experimental approach based on exploitation of the zwitterionic characteristic of amino acid molecules to probe the relative contribution from each. A variety of types of amino acid solutions were adopted to investigate the e...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Zhou R,Nashine V,Palm T,Gandhi R,Adams M

    更新日期:2014-10-01 00:00:00

  • Surface interactions of monoclonal antibodies characterized by quartz crystal microbalance with dissipation: impact of hydrophobicity and protein self-interactions.

    abstract::Surface adsorption of two monoclonal antibodies (mAb1 and mAb2), with widely different hydrophobicity and self-association behavior in solution, was examined by quartz crystal microbalance with dissipation monitoring to understand how adsorption and protein self-interactions near the surface are impacted by their intr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Oom A,Poggi M,Wikström J,Sukumar M

    更新日期:2012-02-01 00:00:00

  • Automated in vitro dissolution rate analysis of potassium in plastic matrix slow release tablets.

    abstract::A fully automated system for dissolution rate analysis of potassium in slow release tablets is described. Aliquots are removed after 1, 2, and 4 hr from six samples, and potassium is analyzed in a flame photometer at 768 nm. A complete study of six samples takes 5.5 hr. The system may be run overnight. During the time...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Engdahl A,Karlberg B,Thelander S

    更新日期:1976-03-01 00:00:00

  • Development of a thermally responsive nanogel based on chitosan-poly(N-isopropylacrylamide-co-acrylamide) for paclitaxel delivery.

    abstract::A thermally responsive nanogel was developed through the radical polymerization based on chitosan (CTS) and N-isopropylacrylamide (NIPAAm) with acrylamide (AAm) blended to explore the possibility of increasing the volume phase transition temperature (VPTT). The thermally sensitive features of resultant nanogels were s...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Wang Y,Xu H,Wang J,Ge L,Zhu J

    更新日期:2014-07-01 00:00:00

  • Fcγ Receptor Activation by Human Monoclonal Antibody Aggregates.

    abstract::Protein aggregates are a potential risk factor for immunogenicity. The measurement, characterization, and control of protein aggregates in drug products are indispensable for the development of biopharmaceuticals, including therapeutic mAbs. In this study, Fcγ receptor (FcγR)-expressing reporter cell lines were used t...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Tada M,Aoyama M,Ishii-Watabe A

    更新日期:2020-01-01 00:00:00

  • Dissolution profiles for finely divided drug suspensions.

    abstract::A suspension of micronized prednisolone acetate was separated into four fractions by the technique of centrifugal elutriation. Data showed that each fraction had a narrow particle size. The dissolution experiments were carried out under sink conditions (less than 10% of saturation concentration) in a dissolution appar...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Mauger JW,Howard SA,Amin K

    更新日期:1983-02-01 00:00:00

  • Development and characterization of a novel, antimicrobial, sterile hydrogel dressing for burn wounds: single-step production with gamma irradiation creates silver nanoparticles and radical polymerization.

    abstract::Patients with burn wounds are susceptible to wound infection and sepsis. This research introduces a novel burn wound dressing that contains silver nanoparticles (SNPs) to treat infection in a 2-acrylamido-2-methylpropane sulfonic acid sodium salt (AMPS-Na(+) ) hydrogel. Silver nitrate was dissolved in AMPS-Na(+) solut...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Boonkaew B,Barber PM,Rengpipat S,Supaphol P,Kempf M,He J,John VT,Cuttle L

    更新日期:2014-10-01 00:00:00

  • A Comparison of Aerosolization and Homogenization Techniques for Production of Alginate Microparticles for Delivery of Corticosteroids to the Colon.

    abstract::Alginate microparticles incorporating hydrocortisone hemisuccinate were produced by aerosolization and homogenization methods to investigate their potential for colonic drug delivery. Microparticle stabilization was achieved by CaCl2 crosslinking solution (0.5 M and 1 M), and drug loading was accomplished by diffusion...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Samak YO,El Massik M,Coombes AGA

    更新日期:2017-01-01 00:00:00

  • Effect of micellization on rate of cupric-ion-promoted hydrolysis of dicarboxylic acid hemiesters.

    abstract::The effect of micellar sodium lauryl sulfate on the rate of cupric-ion-promoted hydrolysis of some dicarboxylic acid hemiesters was investigated at pH 5, ionic strength 0.1 M, and 40, 45, and 50 degrees. The rate of cupric-ion-promoted hydrolysis of sodium n-decyloxalate in the micellar phase is about 50 times as fast...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Ong JT,Kostenbauder HB

    更新日期:1976-12-01 00:00:00

  • Synthesis, cytotoxicity, and phase-solubility study of cyclodextrin click clusters.

    abstract::To explore the possibility of cyclodextrin click clusters (CCCs) as a new cyclodextrin-based excipient, we prepared three different CCCs; heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (HT-β-CD), heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}{2,3-di-O-methyl}-β-cyclodextrin (...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Le HT,Jeon HM,Lim CW,Kim TW

    更新日期:2014-10-01 00:00:00

  • Presystemic metabolism of AZ'0908, a novel mPGES-1 inhibitor: an in vitro and in vivo cross-species comparison.

    abstract::AZ'0908 is a novel microsomal prostaglandin E synthase-1 inhibitor intended for oral administration. Pharmacokinetic experiments in rats showed that bioavailability was much lower than anticipated and increased following pretreatment with the nonspecific cytochrome P450 (CYP) inhibitor 1-aminobenzotriazole, presumably...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Bylund J,Bueters T

    更新日期:2013-03-01 00:00:00

  • Preparation and biological evaluation of tumor-specific Ara-C liposomal preparations containing RGDV motif.

    abstract::Arginine-glycine-aspartate (RGD) has been shown to be essential for the recognition of integrins overexpressed in tumor cells, especially during tumor invasion, angiogenesis, and metasis. In this study, a novel tetrapeptide, RGD-valine (RGDV), was designed and attached to the N position of 1-β-D-arabinofuranosylcytosi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Wang F,Cui C,Ren Z,Wang L,Liu H,Cui G

    更新日期:2012-12-01 00:00:00

  • Hot Melt Extrusion and Spray Drying of Co-amorphous Indomethacin-Arginine With Polymers.

    abstract::Co-amorphous drug-amino acid systems have gained growing interest as an alternative to common amorphous formulations which contain polymers as stabilizers. Several preparation methods have recently been investigated, including vibrational ball milling on a laboratory scale or spray drying in a larger scale. In this st...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Lenz E,Löbmann K,Rades T,Knop K,Kleinebudde P

    更新日期:2017-01-01 00:00:00

  • Properties and stability of a liquid crystal form of cyclosporine-the first reported naturally occurring peptide that exists as a thermotropic liquid crystal.

    abstract::A new solid-state form of cyclosporine produced by spray-drying exhibited characteristics consistent with a liquid crystal. No sharp diffraction peaks were observed by powder X-ray diffraction; however, analysis by both small-angle X-ray diffraction (SAXR) and microscopic under polarized light (PLM) confirmed the exis...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Lechuga-Ballesteros D,Abdul-Fattah A,Stevenson CL,Bennett DB

    更新日期:2003-09-01 00:00:00

  • TLC differentiation of butyrophenone and diphenylbutylpiperidine compounds from phenothiazine derivatives.

    abstract::A procedure is described for TLC detection and differentiation of the butyrophenone-diphenylbutylpiperidine group and phenothiazine derivatives at the microgram level. A two-dimensional TLC method to separate butyrophenone and diphenylbutylpiperidine compounds is reported. A variety of possible detection reagents were...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Pluym A

    更新日期:1979-08-01 00:00:00

  • Thermodynamics of the Enantiotropic Pharmaceutical Compound Benzocaine and Solubility in Pure Organic Solvents.

    abstract::The thermodynamic relationship between FI and FII of ethyl 4-aminobenzoate (benzocaine) has been investigated. Slurry conversion experiments show that the transition temperature below which FI is stable is located between 302 K-303 K (29 °C-30 °C). The polymorphs FI and FII have been characterised by infrared spectros...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Cheuk D,Svärd M,Rasmuson ÅC

    更新日期:2020-11-01 00:00:00

  • Effects of reducing sugars on the chemical stability of human relaxin in the lyophilized state.

    abstract::Sugars and polyols have been used routinely with lyophilized proteins and peptides as bulking agents, cryoprotectants, and lyoprotectants. However, reducing sugars may present a problem as excipients since they are potentially reactive with proteins. In this stability study of recombinant human relaxin (Rix) with vari...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Li S,Patapoff TW,Overcashier D,Hsu C,Nguyen TH,Borchardt RT

    更新日期:1996-08-01 00:00:00