Abstract：
PURPOSE:Previous literature has suggested the absence of an effective barrier between the nasal mucosa and the brain for compounds administered via the nasal route. These experiments were conducted to elucidate the role of the blood-brain barrier efflux transporter P-glycoprotein (P-gp) in attenuating delivery of P-gp substrates to the brain after nasal administration in mice. METHODS:Brain uptake of several radiolabeled P-gp substrates, was measured in P-gp-deficient and P-gp-competent mice following nasal instillation. Additional experiments were performed to assess the potential for enhancing brain uptake by inhibiting P-gp with intranasal rifampin. RESULTS:All substrates examined were measurable in brain tissue within 2 min. Substrate accumulation in P-gp-deficient mice was higher than in P-gp-competent animals; the degree to which P-gp attenuated brain uptake after nasal administration was similar to that during in situ brain perfusion. Co-administration of rifampin enhanced brain uptake of relevant substrates, and resulted in complete elimination of P-gp-mediated transport for 3H- verapamil. CONCLUSIONS:P-gp attenuates brain accumulation of intranasally-administered P-gp substrates. Thus, biochemical components of the blood-brain barrier, such as efflux transporters may influence brain penetration after nasal administration. Co-administration of a P-gp inhibitor enhances the brain uptake of relevant substrates, suggesting that the transporter barrier functions may be reversible.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Graff CL,Pollack GMdoi
10.1023/a:1025053115583subject
Has Abstractpub_date
2003-08-01 00:00:00pages
1225-30issue
8eissn
0724-8741issn
1573-904Xjournal_volume
20pub_type
杂志文章abstract：PURPOSE:To measure the diffusion of nanometer polymersomes through tissue engineered human oral mucosa. METHODS:In vitro models of full thickness tissue engineered oral mucosa (TEOM) were used to assess the penetration properties of two chemically different polymersomes comprising two of block copolymers, PMPC-PDPA an...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9882-6
更新日期：2009-07-01 00:00:00
abstract：PURPOSE:A pattern fitting procedure using X-ray powder diffraction patterns was applied to study the crystallization kinetics of amorphous griseofulvin. From the optimized parameters obtained by pattern fitting, a change in the quantity and quality of griseofulvin crystals with crystallization was also investigated. M...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9204-1
更新日期：2007-05-01 00:00:00
abstract：PURPOSE:Herein we report the discovery of a group of derivatized alpha-amino acids that increase the oral bioavailability of sodium cromolyn. METHODS:We prepared three N-acylated alpha-amino acids and used these compounds to demonstrate the oral delivery of cromolyn in an in vivo rat model. In vitro experiments, inclu...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016034913181
更新日期：1996-02-01 00:00:00
abstract：PURPOSE:To investigate influence of inflammation on metabolism and pharmacokinetics (PK) of midazolam (MDZ) and construct a semi-physiologically based pharmacokinetic (PBPK) model to predict PK in mice with inflammatory disease. METHODS:Glucose-6-phosphate isomerase (GPI)-mediated inflammation was used as a preclinica...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2447-9
更新日期：2018-06-21 00:00:00
abstract：PURPOSE:Effects of polyvinylpyrrolidone (PVP) molecular weight on the solid-state intermolecular interactions among probucol/PVP/sodium dodecyl sulfate (SDS) ternary ground mixtures (GM) and the formation of nanoparticles were investigated by solid-state NMR spectroscopy. MATERIALS AND METHODS:Ternary GMs of probucol ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9089-z
更新日期：2006-11-01 00:00:00
abstract：PURPOSE:For passive dry powder inhalers (DPIs) entrainment and emission of the aerosolized drug dose depends strongly on device geometry and the patient's inhalation manoeuvre. We propose a computational method for optimizing the entrainment part of a DPI. The approach assumes that the pulmonary delivery location of ae...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1992-3
更新日期：2016-11-01 00:00:00
abstract：PURPOSE:The type and relative importance of saturated and unsaturated phospholipid components of surfactant within the epithelial lining fluid (ELF) of the inner and outer surfaces of the lung is not known. METHODS:Seven healthy dogs were anesthetized and a bronchoalveolar lavage (BAL) was performed, immediately follo...
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：PURPOSE:To investigate in vitro if P-glycoprotein (P-gp) transport can differentiate between antibiotic drugs exhibiting increased active renal clearance (CL(r)) in cystic fibrosis (CF) patients (i.e., dicloxacillin, trimethoprim) and drugs that do not exhibit this phenomenon (i.e.. cefsulodin, sulfamethoxazole). METH...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015191511817
更新日期：2002-04-01 00:00:00
abstract：:An on-line simultaneous assay for the enantiomers of verapamil (VA) and its three metabolites in plasma was developed with column-switching HPLC. This system consists of an ovomucoid protein chiral stationary phase coupled to an achiral reversed-phase column via a dilution tube and a trapping column. The reversed-phas...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015848806240
更新日期：1991-08-01 00:00:00
abstract：PURPOSE:Several phenomena in tablets indicate that an inhomogeneous pore distribution is formed during the compaction process. Examples are lamination and the capping of corners. In order to gain an understanding of the relation between structure and compact properties, analyzing the structure in a location dependent m...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-5280-x
更新日期：2005-08-01 00:00:00
abstract：PURPOSE:The purpose of the study was to examine the suitability of using laser diffraction to measure the fine particle fraction (FPF) of drugs emitted from carrier-free dry powder aerosol formulations. MATERIALS AND METHODS:Particle size distribution of terbutaline sulphate from Bricanyl Turbohaler, which contained l...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9056-8
更新日期：2006-09-01 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
abstract：:Dihydropyridine ⇄ pyridinium salt-based brain-selective delivery systems were synthesized for the progestins, ethisterone, norethindrone, and norgestrel. After initial lipophilicity and in vitro studies indicated the feasibility of applying these compounds to brain-specific delivery, in vivo distribution studies were ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016359301852
更新日期：1986-10-01 00:00:00
abstract：PURPOSE:Mannosylation of vaccines is a promising strategy to selectively target vaccine antigens to the mannose receptor expressed on dendritic cells (DCs). The purpose of this study was to investigate the effect of mannan (MN) chemically conjugated to poly(D, L-lactide-co-glycolic acid) (PLGA) nanoparticles (NPs) on a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0459-9
更新日期：2011-09-01 00:00:00
abstract：PURPOSE:We evaluated the effect of luminal bacterial metabolism on intestinal absorption of azetirelin in rats. In vitro characteristics of bacterial metabolism of azetirelin were also investigated with the goal of overcoming the low stability of the peptidic drug against luminal microorganisms. METHODS:Plasma azetire...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012141025938
更新日期：1997-08-01 00:00:00
abstract：PURPOSE:Radial basis function artificial neural networks and theoretical descriptors were used to develop a quantitative structure-pharmacokinetic relationship for structurally diverse drug compounds. METHODS:Human bioavailability values were taken from the literature and descriptors were generated from the drug struc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000012154.09631.26
更新日期：2004-01-01 00:00:00
abstract：PURPOSE:This study was aimed at developing a new active loading method to stably encapsulate staurosporine (STS), a water insoluble drug, into lipid-based nanoparticles (LNPs) for drug targeting to tumors. METHODS:A limited amount of DMSO was included during the active loading process to prevent precipitation and faci...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1854-4
更新日期：2016-05-01 00:00:00
abstract：:The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent wi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015834114359
更新日期：1991-12-01 00:00:00
abstract：PURPOSE:To compare the ability of alkyl-aryl isothiocyanates (ITCs) to increase the activities of the Phase 2 detoxification enzymes NAD[P]H:quinone acceptor oxidoreductase 1 (NQO1) and glutathione S-transferases (GST) in rat tissues in vivo and in cells in vitro. MATERIALS AND METHODS:Twelve alkyl-aryl ITCs and the f...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9595-2
更新日期：2008-09-01 00:00:00
abstract：PURPOSE:A novel bioequivalence limit is proposed taking into account the therapeutic window. METHODS:The therapeutic range is introduced as the ratios maximum tolerated dose/therapeutic dose (MTD/D) and the therapeutic dose/lowest effective dose. The performance of the new acceptance range was compared with the method...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9680-6
更新日期：2008-11-01 00:00:00
abstract：:The effects of skin storage, skin preparation, skin pretreatment with a penetration enhancer, and skin barrier removal by adhesive tape-stripping on the concurrent cutaneous transport and metabolism of nitroglycerin (GTN) have been studied in vitro using hairless mouse skin. Storing the skin for 10 days at 4 degrees C...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015822431178
更新日期：1992-03-01 00:00:00
abstract：PURPOSE:To assess the effects of co-delivering osteoinductive DNA and/or small interfering RNA in directing the osteogenic differentiation of human adipose-derived stem cells (hADSCs) using a combinatorial, non-viral gene delivery approach. METHODS:hADSCs were transfected using combinations of the following genes: BMP...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0406-9
更新日期：2011-06-01 00:00:00
abstract：PURPOSE:To identify materials and processes which effect supersaturation of the GI milieu for low solubility drugs in order to increase oral bioavailability. METHODS:A variety of small and polymeric molecules were screened for their ability to inhibit drug precipitation in supersaturated solutions. The best polymeric ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9852-z
更新日期：2009-06-01 00:00:00
abstract：PURPOSE:Studies were conducted to investigate dilute solutions of the monoclonal antibody (mAb) bevacizumab, mAb fragment ranibizumab and fusion protein aflibercept, develop common procedures for formulation of low concentration mAbs and identify a stabilizing formulation for anti-VEGF mAbs for use in in vitro permeati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2368-7
更新日期：2018-02-28 00:00:00
abstract：:Recently a new in vivo approach in man, using a regional intestinal perfusion technique, has been developed. The perfusion tube consists of a multichannel tube with two inflatable balloons, which are placed 10 cm apart. The tube is introduced orally and the time required for insertion and positioning of the tube is ap...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015888813741
更新日期：1992-10-01 00:00:00
abstract：:(+)-Propranolol was infused at two rates into the pyloric vein (a portal vein tributary) of 15 male Sprague Dawley rats until apparent steady-state conditions were established (i.e., 8 hr at each rate). One group (n = 7) received the high dose (40 micrograms/min/kg) first, and in the other group (n = 8) the low dose (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018921306200
更新日期：1994-03-01 00:00:00
abstract：PURPOSE:4-Phenylbutyrate (4-PBA) is expected to be a potential therapeutic for several neurodegenerative diseases. These activities require 4-PBA transport into the brain across the blood-brain barrier (BBB). The objective of the present study was to characterize the brain transport mechanism of 4-PBA through the BBB. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1912-6
更新日期：2016-07-01 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:Polyethylenimine (PEI) is a highly effective gene delivery vector, but because it is an off-the shelf material, its properties may not be optimal. To investigate the effects of the protonation properties of the polymer, we generated PEI derivatives by acetylating varying fractions of the primary and secondary a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000016251.42392.1e
更新日期：2004-02-01 00:00:00
abstract：:Knowledge of comparative solubility profiles of a base and its hydrochloride salt is important in selecting one form over the other for dosage form design. The studies with two model bases, namely, tiaramide and papaverine, showed that, except during phase transition from a base to a salt or vice versa, the pH-solubil...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016382426347
更新日期：1985-03-01 00:00:00
