Abstract：
:Membrane permeation enhancers have received significant attention in recent years for enabling the oral absorption of poorly permeable drug molecules. In this study, we investigated the ability of His-Ala-Val (HAV) and Ala-Asp-Thr (ADT) peptides derived from the extracellular-1 (EC1) domain of E-cadherin proteins to increase the paracellular permeation and intestinal bioavailability of the poorly permeable model macromolecule, fluorescein-isothiocyanate dextran with average molecular weight 4000 (FD4). The in vitro enzymatic stability of linear and cyclic E-cadherin peptides was characterized under simulated gastric and intestinal conditions, and the cyclic E-cadherin peptides, HAVN1 and ADTC5, which demonstrated excellent stability in vitro, were advanced to in vivo intestinal instillation studies and compared against the established surfactant membrane permeation enhancer, sodium caprate (C10). Cyclic HAVN1 and ADTC5 peptides increased FD4 bioavailability by 7.2- and 4.4-fold compared to control, respectively (not statistically significant). In contrast, C10 provided a statistically significant 10.7-fold relative bioavailability enhancement for FD4. Importantly, this study represents the first report of cyclic E-cadherin peptides as intestinal membrane permeation enhancers. The findings described herein demonstrate the potential of enzymatically stabilized cyclic E-cadherin peptides for increasing poorly permeable drug absorption via the oral route.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Dening TJ,Siahaan TJ,Hageman MJdoi
10.1016/j.xphs.2020.12.018subject
Has Abstractpub_date
2020-12-23 00:00:00eissn
0022-3549issn
1520-6017pii
S0022-3549(20)30830-3pub_type
杂志文章abstract：:The effects of chlorpromazine, prochlorperazine, and trifluoperazine on the pressor actions of serotonin, angiotensin, and bradykinin in the perfused vessels of full-term human placentas were investigated. A significant inhibition of the effect of serotonin was observed with trifluoperazine and chlorpromazine but not ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600651020
更新日期：1976-10-01 00:00:00
abstract：:Particulate matter present in drug products intended for parenteral administration to patients is typically monitored and controlled in the finished drug product to minimize potential risks to patients. In contrast to particulates found in drug products, the current study evaluated particulates representative of mater...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.02.020
更新日期：2019-07-01 00:00:00
abstract：:A crossover experiment was utilized to compare the pharmacokinetics of a 1-g dose of cephalexin tablets, cephalexin capsules, or cephradine capsules in nine normal human volunteers. These antibiotics were administered as three formulations: two 500-mg capsulin every 6 hr for five doses, and one 1000-mg tablet of cepha...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600671033
更新日期：1978-10-01 00:00:00
abstract：:The suppression of imipramine hydrochloride (IMP)- induced hemolysis by native cyclodextrins (alpha-, beta-, and gamma-CDs) and beta-CD derivatives is measured as a function of CD concentration and is quantitatively correlated with the surface tension of the solution determined at 37.0 degrees C. The modified beta-CDs...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.1059
更新日期：2001-08-01 00:00:00
abstract：:In spite of the recent advances in technology to optimize the absorption, distribution, metabolism and elimination (ADME) properties of new and promising medicinal products to reduce clinical failures, the investigation of drug disposition in the pediatric and elderly populations continues to be under evaluated. With ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.22253
更新日期：2011-01-01 00:00:00
abstract：:Gold nanoparticles through nucleation of Au clusters have been extensively studied. However, due to low potency, prolonged tissue retention, and irreversible accumulation, the safety considerations have limited their therapeutic and diagnostic applications. Novel gold nanostructures with retained physical properties a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.02.010
更新日期：2020-05-01 00:00:00
abstract：:Intestinal transport of the type III phosphodiesterase inhibitor cilostazol was characterized to evaluate the influence of secretory transporter. Intestinal absorption of cilostazol measured by the in situ closed loop method, showed regional differences, with high permeability in the upper part of the small intestine....
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10490
更新日期：2003-11-01 00:00:00
abstract：:beta-Cyclodextrin was ethylated at the 2- and 6-hydroxyl positions. Diethyl sulfate was employed as an alkylating reagent. NMR spectra data indicate that heptakis(2,6-di-O-ethyl)-beta-cyclodextrin (DCD) is the principal component of the product obtained. In addition, the FAB mass spectra obtained in nitrobenzyl alcoho...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600840819
更新日期：1995-08-01 00:00:00
abstract：:It has been shown that significant pore induction (electroporation) occurs in human epidermal membrane (HEM) during iontophoresis even at moderate applied voltages (1-10 V). Recent efforts in our laboratory have been aimed at quantifying HEM electroporation by examining the proportionality between flux enhancement due...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.1044
更新日期：2001-07-01 00:00:00
abstract：:Supercritical fluid emulsion extraction is an innovative technology that uses supercritical carbon dioxide (SC-CO(2)) to extract the dispersed oily phase of an emulsion. This technology was used to produce poly-lactic-co-glycolic acid (PLGA) microspheres charged with two common NSAIDs: piroxicam (PX) and diclophenac s...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21920
更新日期：2010-03-01 00:00:00
abstract：:The goal was to evaluate the effects of acidity, expressed as the Hammett acidity function, on chemical reactivity in freeze-dried materials (lyophiles). Dextran-sucrose-citrate and polyvinyl pyrrolidone (PVP)-sucrose-citrate aqueous solutions, adjusted to pH values of 2.6, 2.8, and 3.0 were freeze dried, and characte...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21081
更新日期：2008-01-01 00:00:00
abstract：:This paper traces the academic genealogy of Professor Takeru Higuchi, who is considered "The Father of Physical Pharmacy" because of his contributions to the science of drug formulation and delivery and his impact in mentoring a whole generation of post-World War II pharmaceutical scientists. As one who was mentored b...
journal_title：Journal of pharmaceutical sciences
pub_type： 传,社论,历史文章
doi：10.1002/jps.1049
更新日期：2001-08-01 00:00:00
abstract：:The intrinsic factor-mediated binding of cyanocobalamin to cholestyramine was studied in vitro under varying conditions of pH, added electrolyte, and bile salt. The intrinsic factor-cyanocobalamin complex was adsorbed strongly by the resin at pH 3 in the presence of neutral salt and low concentrations of glycocholic a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600671132
更新日期：1978-11-01 00:00:00
abstract：:High-throughput lyophilization process was designed and developed for protein formulations using a single-step drying approach at a shelf temperature (Ts) of ≥40°C. Model proteins were evaluated at different protein concentrations in amorphous-only and amorphous-crystalline formulations. Single-step drying resulted in...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.11.021
更新日期：2019-04-01 00:00:00
abstract：:Drying is a common pharmaceutical process, whose potential to modify the final drug and/or dosage form properties is often underestimated. In the present study, pellets consisting of the matrix former calcium stearate (CaSt) incorporating the active pharmaceutical ingredient ibuprofen were prepared via wet extrusion a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23707
更新日期：2013-11-01 00:00:00
abstract：:The adsorption of cimetidine on selected pharmaceuticals including kaolin, activated charcoal, talc, and nonsystemic antacids was determined at pH 5.0 and 25 degrees. The Langmuir and Freundlich adsorption isotherms showed that cimetidine adsorption was significant with activated charcoal, kaolin, talc, and magnesium ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600690329
更新日期：1980-03-01 00:00:00
abstract：:The pharmacokinetics and safety of TY-11345 [(+/-)-2-[(4-methoxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9- yl)sulfinyl]-1H-benzimidazole sodium salt], a novel gastric proton pump inhibitor, were studied in healthy male volunteers after single (20, 40, and 80 mg) and repeated oral doses (60 mg, once daily for 7 day...
journal_title：Journal of pharmaceutical sciences
pub_type： 临床试验,杂志文章
doi：10.1002/jps.2600831009
更新日期：1994-10-01 00:00:00
abstract：:Thymopentin (Tp5) was loaded in poly-butylcyanoacrylate (PBCA) nanoparticles (NP) in order to enhance the oral bioavailability of Tp5. PBCA-Tp5-NP was prepared by nanoprecipitation methods. Dialyzing membrane method was employed to examine the in vitro release of PBCA-Tp5-NP in PBS, and Tp5 samples in the release medi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21148
更新日期：2008-06-01 00:00:00
abstract：:The kinetics of decomposition of the following conformationally restricted N-chloro-alpha-amino acids were studied: 1-amino-1-cyclopentanecarboxylic acid (2), 1-amino-1-cyclohexanecarboxylic acid (4), 2-amino-2-norbornanecarboxylic acid (6), and 2-amino-2-benzonorbornanecarboxylic acid (8). The first-order rate consta...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600791216
更新日期：1990-12-01 00:00:00
abstract：:The aim of this study is to explore hot melt extrusion (HME) as a solvent-free drug loading technique for preparation of stable amorphous solid dispersions using mesoporous silica (PSi). Ibuprofen and carvedilol were used as poorly soluble active pharmaceutical ingredients (APIs). Due to the high friction of an API:PS...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.05.039
更新日期：2018-01-01 00:00:00
abstract：:Both nonequilibrium and equilibrium models were proposed to explain the optimal biological response to a set of congeners with respect to the oil-water partition coefficient (P). A detailed analysis of the kinetic model proposed by Hansch demonstrates the bilinear form of the model, with the initial slope of the logar...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600700110
更新日期：1981-01-01 00:00:00
abstract：:A new indole based chalcone molecule MOMIPP induced methuosis mediated cell death in gliobastoma and other cancer cell lines. But the drug was insoluble in water and had a very short plasma half-life. The purpose of this work was to develop a formulation that can provide sustained levels of MOMIPP in vivo. Initial stu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.05.014
更新日期：2020-09-01 00:00:00
abstract：:Although displacement from plasma protein binding (dPB) is usually of little clinical significance, it should be taken into account when interpreting changes in total plasma concentrations of drugs subject to metabolically based drug-drug interactions (mDDI). The aim of this study was to develop an approach to predict...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20733
更新日期：2006-12-01 00:00:00
abstract：:Surfactants stabilize proteins through two major mechanisms: (1) their preferential location at nearby interfaces, in this way precluding protein adsorption; and/or (2) their association with protein into "complexes" that prevent proteins from interacting with surfaces as well as each other. However, selection of surf...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23908
更新日期：2014-05-01 00:00:00
abstract：:A study was undertaken to develop a method that could be used an an indication of the absorption of steroids. It was demonstrated that 17-hydroxycorticosteroids in urine could be quantitatively determined via absorptivity values obtained through the use of standard hydrocortisone-alcohol solutions or standard solution...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640643
更新日期：1975-06-01 00:00:00
abstract：:The hydrophobic substituent parameter for a system of meta- and para-disubstituted benzenes, XC6H4Y, defined as pi X/PhY = log PXC6H4Y - log PC6H5Y, where P is the octanol-water partition coefficient and X and Y are variable and fixed substituents, respectively, varies from one system to another, according to the vari...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720319
更新日期：1983-03-01 00:00:00
abstract：:The binding of representative chemical classes of nonsteroidal anti-inflammatory drugs (NSAIDs) to human serum albumin (HSA) was investigated by equilibrium dialysis. Warfarin enantiomers were used as specific markers in displacement studies. Data were analyzed by a computerized nonlinear least squares approach design...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600770314
更新日期：1988-03-01 00:00:00
abstract：:A sucrose-lactose-starch granulation was used to study particulate motion and attrition in a fluid bed dryer. There is some classification of material in the dryer as drying proceeds; fine particles are dried faster and become less dense, and the less dry but denser large particles show some (although not great) accum...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600641127
更新日期：1975-11-01 00:00:00
abstract：:A method is described for the analysis of amitriptyline, doxepin, imipramine, nortriptyline, desmethyldoxepin, desipramine, and protriptyline in human plasma utlizing GLC-chemical-ionization mass spectrometry with selected ion monitoring. The assay is highly specific and is quantitative to at least 1 ng/ml with a stan...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670106
更新日期：1978-01-01 00:00:00
abstract：:Accurate partition coefficients K = Corg/Caq in chloroform-ammonia can be obtained by measuring the absorbance of the aqueous layer, replenishing with fresh aqueous solvent, and remeasuring the absorption after reequilibration. Provided the solute has a reasonably strong UV absorption, only 0.1-5 mg of material is req...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730222
更新日期：1984-02-01 00:00:00
