Abstract：
PURPOSE:Formulate phospho-sulindac (P-S, OXT-328) in a Pluronic hydrogel to be used as a topical anti-inflammatory agent and study its efficacy, safety and pharmacokinetics in an arthritis model. METHODS:LEW/crlBR rats with Freund's adjuvant-induced arthritis were treated with P-S formulated in Pluronic hydrogel (PSH). We determined the clinical manifestations of arthritis including the locomotor activity of the rats; evaluated joints for inflammation, bone resorption, cartilage damage, COX-2 expression and NF-κB activation; assayed plasma IL-6 and IL-10 levels; and studied the pharmacokinetics of P-S in rats after topical or oral administration. RESULTS:PSH applied at the onset of arthritis or when arthritis was fully developed, suppressed it by 56-82%, improved the locomotor activity of the rats 2.1-4.4 fold, suppressed synovial inflammation, bone resorption, cartilage damage, NF-κB activation and COX-2 expression but not plasma IL-6 and IL-10 levels. There were no side effects. PSH produced rapidly high local levels of P-S with <14% of P-S reaching the circulation, while orally administered P-S was rapidly metabolized generating much lower joint levels of P-S. CONCLUSIONS:Topical application of PSH is efficacious and safe in the treatment of Freund's adjuvant-induced arthritis; has a favorable pharmacokinetic profile; and likely acts by suppressing key pro-inflammatory signaling pathways.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Mattheolabakis G,Mackenzie GG,Huang L,Ouyang N,Cheng KW,Rigas Bdoi
10.1007/s11095-012-0953-8subject
Has Abstractpub_date
2013-06-01 00:00:00pages
1471-82issue
6eissn
0724-8741issn
1573-904Xjournal_volume
30pub_type
杂志文章abstract：PURPOSE:The effect of the molecular weight of dextran on the molecular mobility and protein stability of freeze-dried serum gamma-globulin (BGG) formulations was studied. The stabilizing effect of higher molecular weight dextran is discussed in relation to the molecular mobility of the formulations. METHODS:The molecu...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012194220970
更新日期：1997-06-01 00:00:00
abstract：PURPOSE:The in-situ particle size of delavirdine mesylate in dry mix and tablets was determined. METHODS:Optical microscopy and fluorescence microscopy combined with image analysis were used for qualitative and quantitative measurements. RESULTS:Using optical microscopy, it was demonstrated qualitatively that fragmen...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018875130152
更新日期：1999-04-01 00:00:00
abstract：PURPOSE:A plasmid-based gene expression system was complexed with protective, interactive, and non-condensing (PINC) polymer system and administered with Medi-Jector, a needle-free injection device (NFID), to achieve high and sustained levels of antigen-specific antibodies in blood circulation. METHODS:Human growth ho...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018834305079
更新日期：1999-06-01 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：PURPOSE:To assess the efficacy of lipid-protein-sugar particles (LPSPs) in providing prolonged duration local anesthesia by percutaneous injection. METHODS:Bupivacaine-containing LPSPs were characterized and optimized in vitro. Male Sprague-Dawley rats were given sciatic nerve blocks with bupivacaine-containing LPSPs....
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1026470831256
更新日期：2000-10-01 00:00:00
abstract：:A new enteric-coated formulation of sodium ursodeoxycholate was prepared and administered to man. The barrier film disintegrates and releases the drug only at pH > or = 5.5. The sodium salt of glycoursodeoxycholate was also prepared and encapsulated like ursodeoxycholate. Serum levels of ursodeoxycholate and glycourso...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018907825281
更新日期：1994-05-01 00:00:00
abstract：:An oral formulation of controlled-release isosorbide-5-nitrate pellets has been used to investigate the location of pellets in the gastrointestinal (GI) tract and, in parallel, to measure the drug absorption from these locations. Using the method of gamma scintigraphy the transit times and spreading of pellets in the ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016423404636
更新日期：1987-12-01 00:00:00
abstract：PURPOSE:Cynarin, a potential immunosuppressant that blocks the interaction between the CD28 of T-cell receptor and CD80 of antigen presenting cells, was found in Echinacea purpurea by a new pharmaceutical screening method: After Flowing Through Immobilized Receptor (AFTIR; Dong et al., J Med Chem, 49: 1845-1854, 2006)....
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9754-5
更新日期：2009-02-01 00:00:00
abstract：:Losartan, an antihypertensive agent in clinical development, was found to exist in two enantiotropic polymorphic forms, a low-temperature stable form (Form I) and a high-temperature stable form (Form II), the temperatures at which they are stable being related to the transition temperature. X-ray powder diffraction pa...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018973530443
更新日期：1993-06-01 00:00:00
abstract：PURPOSE:The objective of the current study was to investigate whether blood-brain barrier (BBB) permeability studies in vitro could be accelerated by running several compounds together in the same experiment. METHODS:To address this question, we compared the transport of six compounds run separately with the results o...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000026424.78528.11
更新日期：2004-05-01 00:00:00
abstract：PURPOSE:To employ in vitro experiments combined with computational fluid dynamics (CFD) analysis to determine which aerodynamic factors were most responsible for deaggregating carrier-free powders to form micrometer and submicrometer aerosols from a capsule-based platform. METHODS:Eight airflow passages were evaluated...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1001-z
更新日期：2013-06-01 00:00:00
abstract：PURPOSE:The prognosis for glioma patients is poor, and development of new treatments is critical. Previously, we engineered polymer-based vaccines that control GM-CSF, CpG-oligonucleotide, and tumor-lysate presentation to regulate immune cell trafficking and activation, which promoted potent immune responses against pe...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0361-x
更新日期：2011-05-01 00:00:00
abstract：PURPOSE:This study was conducted to investigate in vivo the impact of interferon-alpha (IFN)-alpha on P-glycoprotein (P-gp) activity in rats by studying how its administration modifies the bioavailability of digoxin, a fairly pure P-gp substrate. METHODS:Human recombinant IFN-alpha was given to rats (n = 5-7 per group...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-7415-5
更新日期：2005-11-01 00:00:00
abstract：PURPOSE:To develop a dose dependent version of BCS and identify a critical dose after which the amount absorbed is independent from the dose. METHODS:We utilized a mathematical model of drug absorption in order to produce simulations of the fraction of dose absorbed (F) and the amount absorbed as function of the dose ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0815-4
更新日期：2012-11-01 00:00:00
abstract：:The role of a bile salt (sodium taurocholate) and lipolysis products (monoglyceride and fatty acid) in the intestinal absorption of a poorly water-soluble drug, diazepam, was investigated. Absorption rates and bioavailabilities were determined with the in situ rat gut technique of Doluisio et al. and analyzing the dia...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016312827680
更新日期：1985-09-01 00:00:00
abstract：PURPOSE:To study the impact of different process conditions and formulation compositions on metastable mannitol forms in protein formulations during lyophilization. METHODS:Mannitol was studied with and without other formulation components. A cryostage was used to mimic the different processing steps during lyophiliza...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0855-9
更新日期：2013-01-01 00:00:00
abstract：PURPOSE:The described structure pharmacokinetic pharmacodynamic relationships (SPPR) study explored the utilization of tetramethylcyclopropane analogues of valpromide (VPD), or tetramethylcyclopropane carboxamide derivatives of valproic acid (VPA) as new antiepileptics. METHODS:The study was carried out by investigati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016055517724
更新日期：1996-02-01 00:00:00
abstract：PURPOSE:Chemically modified heparin-DOCA was prepared and found to have markedly lower anticoagulant activity than heparin. In the present study, we elucidated the antiangiogenic and antitumoral activities of heparin-DOCA derivative. METHODS:To evaluate the antiangiogenic and antitumoral effects of heparin-DOCA, capil...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9139-6
更新日期：2007-01-01 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：:The molecular environment of sucrose and mineral oil within sucrose and mineral oil solid state emulsions was investigated by NMR techniques. The 13C and 1H chemical shifts of sucrose and mineral oil to those observed in solid state emulsions (comprised of sucrose and mineral oil) were equivalent, indicating that the ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018946512445
更新日期：1994-09-01 00:00:00
abstract：:Nasal sprays containing different concentrations of the somatostatin analogue octreotide and sodium tauro-24,25-dihydrofusidate (STDHF) as an absorption promoter were evaluated in two consecutive pharmacokinetic studies in healthy volunteers to characterize their bioavailability and local tolerability. The concentrati...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1023/a:1018927710280
更新日期：1992-01-01 00:00:00
abstract：:Nucleoside transporters play a critical role in the absorption, disposition, and targeting of therapeutically used nucleosides and nucleoside analogs. This review is focused on the Na(+)-dependent, concentrative nucleoside transporters which are found in a variety of cells including renal, intestinal and hepatic epith...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1012113931332
更新日期：1997-11-01 00:00:00
abstract：:One of the authors has his name incorrectly indexed in PubMed and SpringerLink as "Laird Forrest M" (last name "Laird Forrest"). His name should index as "Forrest M. Laird" with last name as "Forrest". ...
journal_title：Pharmaceutical research
pub_type： 杂志文章,已发布勘误
doi：10.1007/s11095-018-2463-9
更新日期：2018-07-25 00:00:00
abstract：PURPOSE:The specific interactions between three lectin-latex conjugates and different structures of rat intestinal mucosa have been studied ex vivo. METHODS:These systems were prepared by covalent coupling of different ligands, i.e., tomato lectin (TL), asparagus pea lectin (AL), mycoplasma gallisepticum lectin (ML), ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016405126656
更新日期：1996-11-01 00:00:00
abstract：PURPOSE:To develop a novel bioadhesive polymer that protects peptide drugs from luminal degradation by aminopeptidase N and to evaluate the system in vitro on porcine mucosa. METHODS:EDTA was covalently bound to chitosan in order to combine the bioadhesive properties of the polymer with the well known capacity of EDTA...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012108118670
更新日期：1997-07-01 00:00:00
abstract：PURPOSE:Heparin immobilized porous poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared for sustained release of basic fibroblast growth factor (bFGF) to induce angiogenesis. MATERIALS AND METHODS:Porous PLGA microspheres having primary amine groups on the surface were prepared using an oil-in-water (O/...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9039-9
更新日期：2006-08-01 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：PURPOSE:Cationic host defence peptides constitute a promising class of therapeutic drug leads with a wide range of therapeutic applications, including anticancer therapy, immunomodulation, and antimicrobial activity. Although potent and efficacious, systemic toxicity and low chemical stability have hampered their comme...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1658-6
更新日期：2015-08-01 00:00:00
abstract：:Sodium taurodihydrofusidate (STDHF) is one of the most promising absorption enhancers for nasal delivery of peptide drugs. Drugs and additives in nasal formulations should not interfere with the self-cleaning capacity of the nose by the ciliary epithelium. Measured in vitro on human adenoid tissue with a photoelectric...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015872617511
更新日期：1990-02-01 00:00:00
abstract：:We describe an assay for acrolein in urine, employing derivatization with m-aminophenol in the presence of ferrous sulfate solution in sulfuric acid. The derivative (7-OH quinoline; DER) and the internal standard (quinine-bisulfate; IS) were separated on a 10-micron particle, 8 mm x 10-cm C18 cartridge in conjunction ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018964401677
更新日期：1993-11-01 00:00:00
