Abstract：
: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.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Mcleod VM,Chan LJ,Ryan GM,Porter CJ,Kaminskas LMdoi
10.1002/jps.24353subject
Has Abstractpub_date
2015-04-01 00:00:00pages
1421-30issue
4eissn
0022-3549issn
1520-6017pii
S0022-3549(15)30165-9journal_volume
104pub_type
杂志文章abstract：:Condensations of carbon disulfide were carried out with amino, chloro, and diamino heterocycles to give condensed ring thiazoline-2-thiones and imidazoline-2-thiones, with cyanomethyl heterocycles to give dithio acid derivatives, and with heterocyclic sulfonamides to give sulfonyldithiocarbamates. Of several examples ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640823
更新日期：1975-08-01 00:00:00
abstract：:With the introduction of Quality by Design (QbD) to the pharmaceutical industry, there has been an increased focus on understanding the nature of particles and composites, with the aim of understanding and modeling how they interact in complex systems, leading to robust dosage forms. Particle characterization tools ha...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.24382
更新日期：2015-05-01 00:00:00
abstract：:Previously, we reported that repeated oral treatment with etoposide (ETP) increased ileal membrane localization of P-glycoprotein (P-gp) and that this was possibly mediated by increased expression of the ezrin/radixin/moesin (ERM)/phosphorylated ERM (p-ERM) via activation of RhoA/ROCK. These changes caused decreases i...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.23503
更新日期：2013-05-01 00:00:00
abstract：:Alginate-based polyelectrolyte complexes (PECs) and hydrogel were engineered as platforms for local bevacizumab (BVZ) therapy. This study provides deep comprehension on the microstructures of such systems, and their correlation with drug-release patterns. PECs and hydrogel were characterized using Fourier transform in...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2018.11.038
更新日期：2019-04-01 00:00:00
abstract：:A sucrose-lactose-starch granulation was used to study particulate motion and attrition in a fluid bed dryer. There is some classification of material in the dryer as drying proceeds; fine particles are dried faster and become less dense, and the less dry but denser large particles show some (although not great) accum...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600641127
更新日期：1975-11-01 00:00:00
abstract：:Three analogs of thyroliberin (I) were prepared. These compounds, N-m-chloroacetylbenzoyl-phenylalanyl-prolineamide (VIa), N-p-chloroacetylbenzoyl-phenylalanyl-prolineamide (VIb) and N-chloroacetyl-alanyl-phenylalanyl-prolineamide (IX), were designed as potential I antagonist affinity labels. However, no significant a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710928
更新日期：1982-09-01 00:00:00
abstract：:The health effects of green tea are associated with catechins: (-)-epigallocatechin-3-O-gallate (EGCG), (-)-epigallocatechin, (-)-epicatechin-3-O-gallate, and (-)-epicatechin. An understanding of compound absorption, distribution, metabolism, excretion, and toxicity characteristics is essential for explaining its biol...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.07.026
更新日期：2018-11-01 00:00:00
abstract：:A sensitive, specific high-performance liquid chromatographic procedure was developed for the determination of plasma ethmozin levels. Basic plasma samples were partitioned with methylene chloride. The organic extract was washed with water and then evaporated to dryness under reduced pressure. The residue was redissol...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600700433
更新日期：1981-04-01 00:00:00
abstract：:Reported estrone pKa and solubility data show wide variation. Improved experimental procedures were designed and used to obtain reproducible results. The pKa values for several estrogens and related compounds also were determined to assess the effects of structural differences on ionization. No evidence was obtained f...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660504
更新日期：1977-05-01 00:00:00
abstract：:In this study, injectable microspheres were developed for the local treatment of joint degeneration in rheumatoid arthritis (RA). Microspheres loaded with triamcinolone (TA), a corticosteroid drug, and/or raloxifene (Ral), a cartilage regenerative drug, were prepared with a biodegradable and biocompatible polymer, pol...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24058
更新日期：2014-08-01 00:00:00
abstract：:The physical state of a dosage form, crystalline versus amorphous, is critical in determining its solid-state physical and chemical properties. This minireview describes the physics associated with the preparation and storage of amorphous solids including a review of the common theories of the glass transition and rel...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.10489
更新日期：2004-01-01 00:00:00
abstract：:The kinetics and pathways for degradation of (+/-)-4'-ethyl-2-methyl-3-(1-pyrrolidinyl)propiophenone hydrochloride (HY-770; 1), a newly developed muscle-relaxing agent, and its analogues were studied in aqueous solution at 50 degrees C, ionic strength 0.5 M, and pH 8.0-12.0. Compound 1 and its four analogues followed ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600780115
更新日期：1989-01-01 00:00:00
abstract：:The metabolic fate of aprophen hydrochloride (2-diethylaminoethyl 2,2-diphenylpropionate) was studied in rats after intravenous administration. Both 14C-labeled and unlabeled aprophen were used in these studies. Blood samples were collected and analyzed to determine the identities of the metabolites formed. Utilizing ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600770210
更新日期：1988-02-01 00:00:00
abstract：:We investigated the effect of cytochrome P450 (CYP) 2C9 polymorphism on the inhibition of methylhydroxylation activity of tolbutamide, a typical CYP2C9 substrate, by triazole antifungal agents, fluconazole and voriconazole. Although the Michaelis constants (Km), maximal velocities (Vmax), and Vmax/Km values for CYP2C9...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.01.007
更新日期：2016-03-01 00:00:00
abstract：:A number of biopharmaceuticals are available as lyophilized formulations along with a prefilled syringe (PFS) containing water for injection (WFI). Submicron- and micron-size droplets of lubricating silicone oil (SO) applied to the inner surface of the PFS barrel might migrate into the WFI, to which protein pharmaceut...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.02.002
更新日期：2019-07-01 00:00:00
abstract：:Specifically tailored amino acid-based formulations were previously shown to have a high potential to avoid stress-mediated degradation of complex molecules such as monoclonal antibodies and viral vectors. By using adenovirus 5 (Ad5) as a model, we studied whether such formulations may also efficiently protect viral v...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.10.063
更新日期：2020-01-01 00:00:00
abstract：:Stirred media milling is the main technology for producing colloidal nanocrystalline suspensions. A number of studies have been reported on the effect of different operating parameters for lab, pilot, and industrial scales. However, typical milling tool box that can be used to support candidate from selection up to ph...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.02.036
更新日期：2017-07-01 00:00:00
abstract：:Complex dosing regimens simulated in the literature using a universal dosing regimen were calculated with a general dosing program developed using the program CONSAM. The program provides a rapid method of calculating nonuniform dosing regimens for up to n = 3 compartments for any linear model. Subject data can also b...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600800406
更新日期：1991-04-01 00:00:00
abstract：:This study determines the enhancing effects of 2-n-nonyl-1,3-dioxolane on the penetration of econazole, an antifungal drug, into the deeper layers of the human nail where fungal infection resides. Aliquots (10 microL) of Econail lacquer formulation containing 0.45 mg of [(14)C]-econazole with 18% 2-n-nonyl-1,3-dioxola...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10291
更新日期：2003-01-01 00:00:00
abstract：:The aim of this article was to prepare a topical powder for the treatment of fungal infections, such as Candida intertrigo and tinea pedis. Thus, an econazole nitrate (ECO) formulation with improved drug dissolution and proper moisture adsorption was designed. ECO was melt with the mesoporous silicate MCM-41 (drug/MCM...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.22183
更新日期：2010-11-01 00:00:00
abstract：:A roadmap for the selection of a pharmaceutical salt form for a development candidate is presented. The free base of the candidate did not have sufficient chemical stability for development. The initially selected salt form turned out to be undevelopable because it was unstable during scale-up synthesis and storage. T...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2017.10.032
更新日期：2018-01-01 00:00:00
abstract：:Flecainide acetate forms acetic acid solvates with 0.5 and 2 acetic acid molecules. Powder X-ray diffraction, differential thermal analysis/thermogravimetric, infrared, and potentiometric titration were used to determine the composition of solvates. Flecainide acetate hemisolvate with acetic acid decomposes to form a ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22295
更新日期：2011-02-01 00:00:00
abstract：:The delivery of active agents to the skin by liposome carriers is an interdisciplinary topic of great interest today. Data accumulated over the last decade strongly point to important advantages of these drug delivery systems. A symposium devoted to classic and new approaches in the use of liposomal systems was organi...
journal_title：Journal of pharmaceutical sciences
pub_type：
doi：10.1002/jps.2600830902
更新日期：1994-09-01 00:00:00
abstract：:The United States Food and Drug Administration recommends pilot dose duration-response and pivotal bioequivalence studies to be conducted using reflectance colorimetry for assessment of the in vivo bioequivalence of topical dermatologic corticosteroids. The major objectives of the present studies were to examine the a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10536
更新日期：2004-01-01 00:00:00
abstract：:Current drug level predictions in nonlinear pharmacokinetics are based on specific pharmacokinetic models in contrast to the model-independent (structureless), dose-linearity, and superposition principles used in linear pharmacokinetics. Such model-dependent methods may not provide reliable predictions due to their in...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730614
更新日期：1984-06-01 00:00:00
abstract：:The quantitative determinations of phenol in phenolated calamine lotion USP and of phenol and resorcinol in phenol-resorcinol-boric acid solution by high-pressure liquid chromatography are reported. The procedures are simple, rapid (no special preliminary treatment is required), and accurate. There is no interference ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600651139
更新日期：1976-11-01 00:00:00
abstract：:(+-)-Carbovir [(+-)-9-[4 alpha-(hydroxymethyl)-cyclopent-2-ene-1 alpha-yl]guanine; NSC 614846] is a novel carbocyclic nucleoside analogue which has been shown to be a potent and selective inhibitor of HIV in vitro. As part of an effort to develop a parenteral formulation for subsequent clinical and toxicological evalu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600790908
更新日期：1990-09-01 00:00:00
abstract：:The synthesis of some substituted 7-hydroxy-5H-1,3,4-oxadiazolo [3,2-a]pyrimidin-5-ones, a class of bicyclics with unexplored pharmacotoxicological properties, is described. Reacting the 2-phenyl derivative with bis(2,4,5-trichlorophenyl)benzylmalonate afforded a linear pyrano-oxadiazolopyrimidinedione. The assigned s...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710210
更新日期：1982-02-01 00:00:00
abstract：:To reduce the risk of immunogenicity that may be caused by therapeutic protein products, it is important to properly characterize subvisible particles and to develop strategies to reduce the levels of particles delivered to patients. In the present study, by using state-of-the-art methods to quantify particle levels, ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.08.022
更新日期：2019-01-01 00:00:00
abstract：:A novel method is described for the preparation of sterile and pyrogen-free submicron liposomes of narrow size distribution. The method is based on the formation of a homogeneous dispersion of lipids in water-soluble carrier materials. To obtain the lipid-containing solid dispersion, liposome-forming lipids and water-...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20055
更新日期：2004-06-01 00:00:00
