Abstract:
PURPOSE:The aim of this study was to investigate transepithelial ionic permeation via the paracellular pathway of human Caco-2 epithelial monolayers and its contribution to absorption of the base guanidine. METHODS:Confluent monolayers of Caco-2 epithelial cells were mounted in Ussing chambers and the transepithelial conductance and electrical potential difference (p.d.) determined after NaCl dilution or medium Na substitution (bi-ionic conditions). Guanidine absorption (Ja-b) was measured +/- transepithelial potential gradients using bi-ionic p.d.'s. RESULTS:Basal NaCl replacement with mannitol gives a transepithelial dilution p.d. of 28.0 +/- 3.1 mV basal solution electropositive (PCl/PNa = 0.34). Bi-ionic p.d.'s (basal replacements) indicate a cation selectivity of NH4+ > K+ approximately Cs+ > Na+ > Li+ > tetraethylammonium+ > N-methyl-D: -glucamine+ approximately choline+. Transepithelial conductances show good correspondence with bi-ionic potential data. Guanidine Ja-b was markedly sensitive to imposed transepithelial potential difference. The ratio of guanidine to mannitol permeability (measured simultaneously) increased from 3.6 in the absence of an imposed p.d. to 13.8 (basolateral negative p.d.). CONCLUSIONS:Hydrated monovalent ions preferentially permeate the paracellular pathway (Eisenman sequence 2 or 3). Guanidine may access the paracellular pathway because absorptive flux is sensitive to the transepithelial potential difference. An alternative method to assess paracellular-mediated flux of charged organic molecules is suggested.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Carr G,Haslam IS,Simmons NLdoi
10.1007/s11095-006-9568-2subject
Has Abstractpub_date
2006-03-01 00:00:00pages
540-8issue
3eissn
0724-8741issn
1573-904Xjournal_volume
23pub_type
杂志文章abstract:PURPOSE:The purpose of this study was to use a replicate designed trial to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters of CGP 33101 after oral administration of tablets relative to that of powder suspended in water, and to determine the relative proportion of the intra-subje...
journal_title:Pharmaceutical research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1016275402723
更新日期:1995-12-01 00:00:00
abstract:PURPOSE:To determine whether LHRH-receptor is expressed in Calu-3, a human bronchial epithelial cell line, and to further determine whether this receptor plays a role in the transport of deslorelin, an LHRH agonist. METHODS:Using cultured monolayers of Calu-3 grown at air-interface, the presence and localization of LH...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000029294.70707.74
更新日期:2004-06-01 00:00:00
abstract:PURPOSE:The purpose of this study was to determine the potential effect of probenecid on the pharmacokinetics of zalcitabine in HIV-positive patients. METHODS:Twelve patients received single oral 1.5 mg doses of zalcitabine alone and during probenecid treatment (500 mg at 8 and 2 hours before and 4 hours after zalcita...
journal_title:Pharmaceutical research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1016009029536
更新日期:1996-03-01 00:00:00
abstract::Defined size fractions of polyethyleneglycol powder (MW = 10,000) were mixed with defined size fractions of alpha-lactose monohydrate in order to study the effect of compaction as a function of the weight ratios of the two excipients. For a precise control of the compression cycle, tablets were compressed on a Univers...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015864415693
更新日期:1990-02-01 00:00:00
abstract:OBJECTIVES:We recently demonstrated that fibrin-based tissue engineered blood vessels (TEV) exhibited vascular reactivity, matrix remodeling and sufficient strength for implantation into the veins of an ovine animal model, where they remained patent for 15 weeks. Here we present an approach to improve the mechanical pr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9499-6
更新日期:2008-05-01 00:00:00
abstract:PURPOSE:The trial-and-error approach is still predominantly used in pharmaceutical development of nanosuspensions. Physicochemical dispersion stability is a primary focus and therefore, various analytical bulk methods are commonly employed. Clearly less attention is directed to surface changes of nanoparticles even tho...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2300-6
更新日期:2018-02-21 00:00:00
abstract:PURPOSE:The purpose of this study was to investigate the effects of formulation factors including varying wax concentration, drug loading and drug particle size, on drug release characteristics from both pure oil and gel formulations prepared with a combination of derivatized vegetable oil (Labrafil 1944 CS) and glycer...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016209020160
更新日期:1995-06-01 00:00:00
abstract:PURPOSE:To evaluate the potential of ascorbate as a novel ligand in the preparation of pharmaceutical nanocarriers with enhanced tumor-cell specific binding and cytotoxicity. METHODS:Palmitoyl ascorbate was incorporated into liposomes at varying concentrations. A stable formulation was selected based on size and zeta ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9674-4
更新日期:2008-11-01 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:Excipients are added to lyophilized protein drug formulations to protect the protein during processing and storage, but the mechanisms are poorly understood. Here, hydrogen/deuterium (H/D) exchange with mass spectrometry was used to assess protein conformation and excipient interactions in lyophilized solids. ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9365-6
更新日期:2008-02-01 00:00:00
abstract:PURPOSE:To determine the factors influencing "solid solubility" and phase separation kinetics of drugs from amorphous solid dispersions. METHODS:Solid dispersions of griseofulvin-poly(vinyl pyrrolidone) (PVP) and indoprofen-PVP were prepared using solvent evaporation technique. Dispersions demonstrating single Tg were...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-004-1882-y
更新日期:2005-03-01 00:00:00
abstract:PURPOSE:Carboxylesterases are important in the detoxification of drugs, pesticides and other xenobiotics. This study was to evaluate a series of substrates and inhibitors for characterizing these enzymes. METHODS:A series of novel aliphatic esters and thioesters were used in spectral assays to monitor human, murine an...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016071311190
更新日期:1996-10-01 00:00:00
abstract:PURPOSE:The aim of the present study was to improve the dry powder inhalation behavior of steroid KSR-592 with lactose by altering the crystal shape and the particle size of the drug for use in a newly designed inhalation device, Jethaler. METHOD:The shape of the crystals was changed by polymorphic transformation of o...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1020492213172
更新日期:2002-10-01 00:00:00
abstract:PURPOSE:The heats of reaction between the enantiomers and racemates of ibuprofen and naproxen and human serum albumin (HSA) are to be measured with and without the addition of octanoic acid. The effects of octanoic acid on the free energies of interaction between the drugs and HSA is to be determined and compared to th...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016066325476
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:Knowledge about the uptake mechanism and subsequent intracellular routing of non-viral gene delivery systems is important for the development of more efficient carriers. In this study we compared two established cationic polymers pDMAEMA and PEI with regard to their transfection efficiency and mechanism of cell...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9287-3
更新日期:2007-08-01 00:00:00
abstract:PURPOSE:In vitro in vivo correlation (IVIVC) is a biopharmaceutical tool recommended for use in formulation development. When validated, IVIVC can be used to set dissolution limits and, based on the dissolution limits, as a surrogate for an in vivo study. The purpose of this paper is to study the various methods used t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1349-8
更新日期:2014-09-01 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::The mechanical properties of dry and wet polymeric films prepared from various aqueous polymeric dispersions were evaluated by a puncture test. They were studied with respect to type of polymer dispersion [cellulosic: Aquacoat and Surelease; acrylic: Eudragit NE, L, RS, and RL 30 D], plasticizer type (water-soluble or...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018942127524
更新日期:1994-06-01 00:00:00
abstract:PURPOSE:To describe a computational tool to calculate molecular descriptors of potential application in ADME virtual screening of antitumor Pt(II) drug candidates. METHODS:The multistep computational procedure consists in (a) building and optimization (PM3) of the 3D structures of the investigated complexes, (b) param...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0317-1
更新日期:2011-03-01 00:00:00
abstract::At an ever increasing pace, synthetic biomaterials are being developed with specific functionalities for tissue engineering applications. These biomaterials possess properties including biocompatibility, mechanical strength, and degradation as well as functionalities such as specific cell adhesion and directed cell mi...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-008-9620-5
更新日期:2008-10-01 00:00:00
abstract::One of the barriers to transdermal delivery of peptides is the metabolic activity of the epidermis. To define this metabolic activity, aminopeptidase activity and Leu-enkephalin metabolism were measured in the epidermis obtained from neonatal mouse skin and in cultured mouse keratinocytes. Aminopeptidase activity was ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015882323677
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:Microphysiological systems (MPS), also known as "organs-on-chips" or "tissue chips," leverage recent advances in cell biology, tissue engineering, and microfabrication to create in vitro models of human organs and tissues. These systems offer promising solutions for modeling human physiology and disease in vitr...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-019-2742-0
更新日期:2019-12-17 00:00:00
abstract:PURPOSE:The possibility of direct delivery of steroids through the skin to the trachea and the effect of iontophoresis on delivery efficacy were evaluated after the application of an ionic steroidal prodrug, prednisolone sodium succinate (PS-Na), to the throat skin. METHODS:Fluorescein sodium salt (FL-Na) and PS-Na we...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0337-x
更新日期:2011-04-01 00:00:00
abstract::The effect of freezing on formation of soluble and insoluble aggregates of human growth hormone (hGH) was studied. The amount of soluble aggregates was affected very little by freezing regardless of the cooling rate. In contrast, the formation of insoluble aggregates (particulates), as determined by light scattering i...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015888704365
更新日期:1991-11-01 00:00:00
abstract::Growing tumors develop additional new blood vessels to meet the demand for adequate nutrients and oxygen, a process called angiogenesis. Cancer is a highly complex disease promoted by excess angiogenesis; interfering with this process poses for an attractive approach for controlling tumor growth. This hypothesis led t...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-008-9634-z
更新日期:2008-12-01 00:00:00
abstract::A quantitative analysis of the dependence of dissolution rate on the relative surface area occupied by two non-interacting drug mixtures from co-compressed slabs is described. The results from the experimental dissolution rates of each component from naproxen/phenytoin co-compressed slabs under laminar flow conditions...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018979419714
更新日期:1994-10-01 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::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
pub_type: 杂志文章
doi:10.1023/a:1015826229323
更新日期:1990-03-01 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:Modulation of 5-HT3 receptor in the central nervous system (CNS) is a promising approach for treatment of neuropathic pain. The goal was to evaluate the role of P-glycoprotein (Pgp) in limiting exposure of different parts of the CNS to ondansetron (5-HT3 receptor antagonist) using wild-type and genetic knockout...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02929-2
更新日期:2020-09-28 00:00:00