Abstract：
PURPOSE:To determine whether a Protected Graft Copolymer (PGC) containing fatty acid can be used as a stabilizing excipient for GLP-1 and whether PGC/GLP-1 given once a week can be an effective treatment for diabetes. METHODS:To create a PGC excipient, polylysine was grafted with methoxypolyethyleneglycol and fatty acid at the epsilon amino groups. We performed evaluation of the binding of excipient to GLP-1, the DPP IV sensitivity of GLP-1 formulated with PGC as the excipient, the in vitro bio-activity of excipient-formulated GLP-1, the in vivo pharmacokinetics of excipient-formulated GLP-1, and the efficacy of the excipient-formulated GLP-1 in diabetic rats. RESULTS:We showed reproducible synthesis of PGC excipient, high affinity binding of PGC to GLP-1, slowed protease degradation of excipient-formulated GLP-1, and that excipient-formulated GLP-1 induced calcium influx in INS cells. Excipient-formulated GLP-1 stays in the blood for at least 4 days. When excipient-formulated GLP-1 was given subcutaneously once a week to diabetic ZDF rats, a significant reduction of HbA1c compared to control was observed. The reduction is similar to diabetic ZDF rats given exendin twice a day. CONCLUSIONS:PGC can be an ideal in vivo stabilizing excipient for biologically labile peptides.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Castillo GM,Reichstetter S,Bolotin EMdoi
10.1007/s11095-011-0542-2subject
Has Abstractpub_date
2012-01-01 00:00:00pages
306-18issue
1eissn
0724-8741issn
1573-904Xjournal_volume
29pub_type
杂志文章abstract：:Biotherapeutics, including recombinant or plasma-derived human proteins and antibody-based molecules, have emerged as an important class of pharmaceuticals. Aggregation and immunogenicity are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0414-9
更新日期：2011-05-01 00:00:00
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)...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0953-8
更新日期：2013-06-01 00:00:00
abstract：:To evaluate the effects of a neutron activation radiolabeling technique on an enteric-coated multiparticulate formulation of erythromycin, test quantities were produced under industrial pilot scale conditions. The pellets contained the stable isotope erbium oxide (Er-170), which was later converted by neutron activati...
journal_title：Pharmaceutical research
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doi：10.1023/a:1015826229323
更新日期：1990-03-01 00:00:00
abstract：PURPOSE:To elucidate the apical and basolateral components of the total unstirred water layer in regular permeability experiment. METHODS:A novel stirring apparatus was constructed to remove the basolateral unstirred water layer. Caco-2 cells were used as the permeability barrier both in Transwell-type and side-by-sid...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9573-8
更新日期：2008-07-01 00:00:00
abstract：:Four lipophilic, low molecular weight drugs solubilized in phosphatidylcholine-bile salt mixed micelles were injected s.c. into the hind legs of sheep and their cumulative recoveries in lymph draining from the site of application were determined. Surprisingly, the cumulative recoveries (percentage of dose) varied betw...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015807913934
更新日期：1991-10-01 00:00:00
abstract：:A number of substituted phthalimide, 1, 8-naphthalimide, succinimide and glutarimide derivatives demonstrated significant hypolipidemic activity at 20 mg/kg/ day, I.P. after 16 days dosing. The N-(n-pentyl) succinimide proved to be the most potent analogue of the new compounds, lowering serum triglyceride levels 51 % ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016346018962
更新日期：1984-11-01 00:00:00
abstract：PURPOSE:Tumor vascular normalization by antiangiogenic agents may increase tumor perfusion but reestablish vascular barrier properties in CNS tumors. Vascular priming via nanoparticulate carriers represents a mechanistically distinct alternative. This study investigated mechanisms by which sterically-stabilized liposom...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0823-4
更新日期：2012-12-01 00:00:00
abstract：PURPOSE:The purpose of this study was to establish a useful methodology, possibly providing information on the stoichiometry of pharmaceutical drug salts obtained from salt screening by using a multiwell plate and a Raman microscope. METHODS:Tamoxifen salt screening was conducted with monobasic and polybasic acids on ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9644-7
更新日期：2006-04-01 00:00:00
abstract：:Physiologically-based pharmacokinetic (PBPK) models explicitly incorporate tissue-specific blood flows, partition coefficients, and metabolic processes. Since PBPK models are derived using physiologic parameters and interactions of the compound with tissue components, these models are considered to be "bottom up" as o...
journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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doi：10.1023/a:1015941706008
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abstract：PURPOSE:S-(4-Nitrobenzyl)-6-thioinosine (NBMPR) is routinely used at concentrations of 0.10 μM and 0.10 mM to specifically inhibit transport of nucleosides mediated by equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2), respectively. We recently showed that NBMPR (0.10 mM) might also inhibit placental active e...
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doi：10.1007/s11095-020-2782-5
更新日期：2020-02-21 00:00:00
abstract：PURPOSE:To examine the changes in expression levels of CYP3A4 and efflux transporters in CYP3A4-transfected Caco-2 (colon carcinoma) cells in the presence of the inducers sodium butyrate (NaB) and 12-O-tetradecanoylphorbol-13-acetate (TPA). To characterize the transport of [3H]-digoxin and the metabolism of midazolam i...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1010914624111
更新日期：2001-08-01 00:00:00
abstract：PURPOSE:Cell penetrating peptides (CPPs) were widely used as motifs for drug delivery to tumor. In former study, an RGD reverse sequence dGR was used to develop active-targeting liposome R8dGR-Lip, which showed well penetrating ability and treatment efficiency on glioma model. However, recurrence after tumor resection ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2399-0
更新日期：2018-04-26 00:00:00
abstract：PURPOSE:To develop a semi-mechanistic population pharmacokinetic model based on gastric emptying function for acetaminophen plasma concentration in critically ill patients tolerant and intolerant to enteral nutrition before and after prokinetic therapy. METHODS:Acetaminophen plasma concentrations were available from a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0290-8
更新日期：2011-02-01 00:00:00
abstract：:Apigenin, a naturally occurring plant flavone, abundantly present in common fruits and vegetables, is recognized as a bioactive flavonoid shown to possess anti-inflammatory, antioxidant and anticancer properties. Epidemiologic studies suggest that a diet rich in flavones is related to a decreased risk of certain cance...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-010-0089-7
更新日期：2010-06-01 00:00:00
abstract：PURPOSE:The use of "Trojan Horse" nanocarriers for antibiotics to enhance the activity of antibiotics against susceptible and resistant bacteria is investigated. METHODS:Antibiotic carriers (CD-MAN and CD-GLU) are prepared from β-cyclodextrin grafted with sugar molecules (D-mannose and D-glucose, respectively) via azi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1861-0
更新日期：2016-05-01 00:00:00
abstract：PURPOSE:The purpose of this study was to evaluate the feasibility of delivering vapreotide, a somatostatin analogue, by transdermal iontophoresis. METHODS:In vitro experiments were conducted using dermatomed porcine ear skin and heat-separated epidermis. In addition to quantifying vapreotide transport into and across ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-5276-6
更新日期：2005-08-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1018-3
更新日期：2013-07-01 00:00:00
abstract：PURPOSE:Performance of a transdermal delivery system (TDS) can be affected by exposure to elevated temperature, which can lead to unintended safety issues. This study investigated TDS and skin temperatures and their relationship in vivo, characterized the effective thermal resistance of skin, and identified the in vitr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2171-x
更新日期：2017-07-01 00:00:00
abstract：PURPOSE:The rapid oxidation of rofecoxib under alkaline conditions has been previously reported. The oxidation was reported to involve gamma-lactone ring opening to an alcohol, which further oxidized to a dicarboxyclic acid. The oxidation was suspected to be mediated by peroxy radicals. This work further investigates t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-6947-z
更新日期：2005-10-01 00:00:00
abstract：PURPOSE:To evaluate 26 marketed oncology drugs for time-dependent inhibition (TDI) of cytochrome P450 (CYP) enzymes. Evaluate TDI-positive drugs for potential to generate reactive intermediates. Assess clinical drug-drug interaction (DDI) risk using static mechanistic models. METHODS:Human liver microsomes and CYP-spe...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0724-6
更新日期：2012-07-01 00:00:00
abstract：:Enoximone and piroximone are cardiotonic agents for use in patients with congestive heart failure. Electroanalytical studies revealed that the dihydroimidazolone functionality was oxidizable and that this property can be analytically useful. The compounds undergo a two-electron, irreversible oxidation in neutral to ac...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015811830830
更新日期：1991-07-01 00:00:00
abstract：PURPOSE:To evaluate the use of an in vitro intestinal permeability model to predict rat and human absorption as well as to evaluate the use of an internal standard to control for intra- and inter-rat variability. METHODS:In vivo peroral absorption and in vitro steady-state intestinal permeability coefficients were det...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012148300807
更新日期：1997-12-01 00:00:00
abstract：PURPOSE:Reverse iontophoresis is an alternative to blood sampling for the monitoring of endogenous molecules. Here, the potential of the technique to measure urea and potassium levels non-invasively, and to track their concentrations during hemodialysis, has been examined. MATERIALS AND METHODS:In vitro experiments we...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9237-0
更新日期：2007-06-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-7677-y
更新日期：2005-11-01 00:00:00
abstract：:The effect of the penetration enhancers Azone, oleic acid, 1-dodecanol, dodecyl N,N-dimethylaminoacetate (DDAA), and dodecyl N,N-dimethylaminoisopropionate (DDAIP) on epithelial membrane lipids was examined using human buccal cell membranes as a model for epithelial lipid bilayer. Buccal epithelial cells (BEC) were la...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018919811227
更新日期：1994-02-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012084207399
更新日期：1997-02-01 00:00:00
abstract：PURPOSE:The acne skin is characteristic of a relatively lower pH microenvironment compared to the healthy skin. The aim of this work was to utilize such pH discrepancy as a site-specific trigger for on-demand topical adapalene delivery. METHODS:The anti-acne agent, adapalene, was encapsulated in acid-responsive polyme...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1398-z
更新日期：2014-11-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9783-0
更新日期：2009-04-01 00:00:00
abstract：PURPOSE:Biomaterials which release locally high concentrations of antithrombotic agents should lessen the thrombogenicity of the materials. To evaluate this approach, we prepared novel polyurethane matrices loaded with hirudin and coated them with 2-hydroxyethyl methacrylate (HEMA) by glow discharge plasma deposition (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011987423502
更新日期：1998-05-01 00:00:00
