Abstract:
PURPOSE:To prepare acylated exenatide analogues and investigate their biological properties for guiding the development of PLGA formulations of exenatide. METHODS:The acylated exenatide analogues were prepared by reaction with glycolic acid (GA), one constitutional unit of PLGA, and characterized by HPLC-MS/MS and Circular Dichroism (CD). The pharmacokinetic properties and anti-diabetic activities were studied in SD rats and db/db mice, respectively. RESULTS:Structural characterizations of the acylated products showed that one to four glycolic acids (GAs) were connected to the primary amine groups of exenatide, and there was a conversion of α-helix to β-sheet to some extent. Pharmacokinetic studies in SD rats revealed that acylated exenatides had a similar Tmax with that of the prototype drug, whereas the Cmax and the AUC values of the adducts were significantly decreased. Biological activity tests demonstrated that exenatide and acylated exenatide analogues had similar in vivo antidiabetic activities in terms of controlling blood glucose concentration, HbA1c level, body weight and food intake. CONCLUSIONS:These findings suggest that GA conjugated exenatide had no influence on the peptide efficacy, therefore it's not necessary to inhibit exenatide acylation in PLGA formulations during the peptide release process.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Liang R,Li X,Zhang R,Shi Y,Wang A,Chen D,Sun K,Liu W,Li Ydoi
10.1007/s11095-014-1298-2subject
Has Abstractpub_date
2014-08-01 00:00:00pages
1958-66issue
8eissn
0724-8741issn
1573-904Xjournal_volume
31pub_type
杂志文章abstract:PURPOSE:The feasibility of using iontophoresis to enhance the permeation rate of a model peptide was investigated in vitro using hairless mouse skin. METHODS:Angiotensin 2 (AT 2) was employed as a permeant probe, using optimum iontophoresis conditions. A number of physicochemical parameters (donor ionic strength; vale...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016254230155
更新日期:1995-07-01 00:00:00
abstract::The effects of tertiary amine-containing basic drugs on the enzymes located in the mitochondria and the effect of monoamine oxidase inhibitors (MAOIs) on drug accumulation in lung mitochondria have been studied. Various basic drugs inhibited MAO activity but not other mitochondrial marker enzymes. The potency of MAO i...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015964623098
更新日期:1989-10-01 00:00:00
abstract:PURPOSE:Short linear peptides have a high potential for delivering various drugs with therapeutic potential, including nucleic acids. Recently, we have shown that the cationic amphipathic histidine-rich peptide LAH4 (KKALLALALHHLAHLALHLALALKKA) possesses high plasmid DNA delivery capacities. Since such peptides are tho...
journal_title:Pharmaceutical research
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doi:10.1007/s11095-010-0138-2
更新日期:2010-07-01 00:00:00
abstract:PURPOSE:Type I collagen accumulates during liver fibrosis primarily because α-complex protein-2 (αCP(2)), encoded by the poly(rC) binding protein 2 (PCBP2) gene, binds to the 3' end of the collagen mRNA and increases its half-life. This study aimed to reverse the pro-fibrogenic effect of alcohol on hepatic stellate cel...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0475-9
更新日期:2011-12-01 00:00:00
abstract::Nanobiosensors with high sensitivity and specificity have shown great potential in the detection of diseases. The incorporation of therapeutic agents with nanobiosensors allows the simultaneous diagnosis and therapy of diseases. The delivery of nanobiosensors and therapeutic agents using polymers is a common strategy ...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-016-1944-y
更新日期:2016-10-01 00:00:00
abstract:PURPOSE:The purpose of this study was to stabilize the vinca alkaloids, vincristine sulfate (VCR) and vinblastine sulfate (VBL), in poly(lactide-co-glycolide) (PLGA) microspheres and to release the drugs in a sustained manner for more than a month. METHODS:An oil-in-oil emulsion-solvent extraction method was used to e...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1007522013835
更新日期:2000-06-01 00:00:00
abstract:PURPOSE:This study addresses the effect of freezing and thawing on a therapeutic monoclonal antibody (mAb) solution and the corresponding buffer formulation. Particle formation, crystallization behaviour, morphology changes and cryo-concentration effects were studied after varying the freezing and thawing rates, buffer...
journal_title:Pharmaceutical research
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doi:10.1007/s11095-018-2378-5
更新日期:2018-03-19 00:00:00
abstract:PURPOSE:For determination of the transit time through various parts of the gastrointestinal (GI) tract, we developed a method that provides the location of disintegration and drug release. This method involves GI magnetomarkergraphy (GIMG) using a 129-channel Shimadzu vector biomagnetic measurement system (BMS). METHO...
journal_title:Pharmaceutical research
pub_type: 临床试验,杂志文章
doi:10.1023/a:1007561129221
更新日期:2000-02-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012161630481
更新日期:1997-08-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1750-y
更新日期:2015-12-01 00:00:00
abstract:PURPOSE:Since the absorption of ceftriaxone (CTO) in the intestine is restricted by its natural physiological characteristics, we developed a series of small synthetic compounds derived from bile acids to promote the absorption of CTO in the gastrointestinal tract. METHODS:Several bile acid derivatives were screened b...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0932-0
更新日期:2013-04-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9934-0
更新日期:2006-05-01 00:00:00
abstract:PURPOSE:Evidence suggests that uremic toxins such as hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS), and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) promote the progression of renal failure by damaging tubular cells via rat organic anion transporter 1 (rOat1) and rOat3 on the basolateral membrane of ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-2486-x
更新日期:2005-04-01 00:00:00
abstract:PURPOSE:To group microcrystalline celluloses (MCCs) using a combination of artificial neural network (ANN) and data clustering. METHODS:Radial basis function (RBF) network was used to model the torque measurements of the various MCCs. Output from the RBF network was used to group the MCCs using a data clustering techn...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-004-7690-6
更新日期:2004-12-01 00:00:00
abstract:PURPOSE:To evaluate the effect of re-directing the uptake mechanism of polyplexes containing oligodeoxynucleotide (ODN) decoys to nuclear factor kappa B (NF-kappaB) from absorptive-mediated to receptor-mediated endocytosis. MATERIALS AND METHODS:Complexes of ODNs and a co-polymer of biotin-polyethylenglycol and polyet...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9389-y
更新日期:2008-03-01 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:PURPOSE:To co-crystallise mannitol and lactose with a view to obtaining crystals with more favourable morphological features than either lactose or mannitol alone, suitable for use as carriers in formulations for dry powder inhalers (DPIs) using simultaneous engineering of lactose-mannitol mixtures. METHODS:Mannitol a...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0743-3
更新日期:2012-08-01 00:00:00
abstract:PURPOSE:Orthorhombic crystals of paracetamol exhibit good technological properties during compression. The purpose of this study was to investigate the compression behavior of this substance and to compare it to that of monoclinic paracetamol. From the crystal structure, it could be hypothesized that sliding planes are...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011954800246
更新日期:1998-07-01 00:00:00
abstract:PURPOSE:This study uses high drug content solid dispersions for dose window extension beyond current demonstrations using fused deposition modelling (FDM) to; i) accommodate pharmaceutically relevant doses of drugs of varying potencies at acceptable dosage form sizes and ii) enable enhanced dose flexibility via modular...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2720-6
更新日期:2019-12-17 00:00:00
abstract::A new high-performance liquid chromatographic (HPLC) assay suitable for pharmacokinetic studies of enantiomers of fenoprofen (FEN) was developed. Following the addition of internal standard (IS; racemic ketoprofen), the plasma or urine constituents are extracted into a mixture of isooctane:isopropanol (95:5), back ext...
journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:1988-01-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-5277-5
更新日期:2005-08-01 00:00:00
abstract:PURPOSE:To investigate the potential of chitosan nanoparticles as a system for improving the systemic absorption of insulin following nasal instillation. METHODS:Insulin-loaded chitosan nanoparticles were prepared by ionotropic gelation of chitosan with tripolyphosphate anions. They were characterized for their size a...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018908705446
更新日期:1999-10-01 00:00:00
abstract:PURPOSE:The aim of the study is to determine the effect of experimental parameters on microinfusion through hollow microneedles into skin to optimize drug delivery protocols and identify rate-limiting barriers to flow. METHODS:Glass microneedles were inserted to a depth of 720-1080 microm into human cadaver skin to mi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-8498-8
更新日期:2006-01-01 00:00:00
abstract:PURPOSE:Adenoviruses are being developed for diseases of the gastrointestinal tract. Several in vitro assays were used to predict stability of PEGylated adenovirus along the GI tract and determine in vivo gene transfer after oral administration. METHODS:Recombinant adenovirus was modified with monomethoxypoly(ethylene...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1025714412337
更新日期:2003-09-01 00:00:00
abstract:PURPOSE:The aim was to replace the traditional 21-day Caco-2 permeability protocol by a more high-throughput assay. METHODS:Caco-2 cells were seeded at high density in 96-well plates in novel cell culture boxes. After 7 days, drug permeability studies were performed. Samples were analyzed by a new UV detection method....
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000008043.71001.43
更新日期:2003-12-01 00:00:00
abstract::This paper describes an investigation of the use of poly(lactic/glycolic acid) polymers for long-term delivery of high molecular weight, water-soluble proteins. Poly(lactic/glycolic acid) (PLGA) microspheres, containing (fluorescein isothiocyanate)-labeled bovine serum albumin and (fluorescein isothiocyanate)-labeled ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015841715384
更新日期:1991-06-01 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::The interdependent relationship between pharmacology and toxicology is fundamental to the concepts of efficacy and safety of both drugs and xenobiotics. The traditional concept of establishing efficacious and tolerated doses to define a 'therapeutic window' appears simplistic in the context of an exponentially increas...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
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更新日期:2014-09-01 00:00:00
abstract:PURPOSE:To show that atomic force microscopy (AFM) can be used to directly study the electrostatic charging and dissipation of single pharmaceutical particles. MATERIALS AND METHODS:Particles of lactose attached to AFM cantilevers were charged on a glass surface at a relative humidity (RH) of 0.1%. By recording force-...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9230-z
更新日期:2007-06-01 00:00:00
abstract:PURPOSE:Phase II metabolism involves the conjugation of a polar moiety, such as sulfate or glucuronic acid, to a (relatively) nonpolar xenobiotic. Although it might be expected that such conjugates may exhibit amphiphilic character (e.g., surface activity and potential to form micelles), no detailed study of the micell...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1022672608657
更新日期:2003-03-01 00:00:00