Abstract：
:In order to study the influence of hydrogen bonding in the amide backbone of a peptide on permeability across a cell membrane, a series of tetrapeptide analogues was prepared from D-phenylalanine. The amide nitrogens in the parent oligomer were sequentially methylated to give a series containing from one to four methyl groups. The transport of these peptides was examined across confluent monolayers of Caco-2 cells as a model of the intestinal mucosa. The results of these studies showed a substantial increase in transport with each methyl group added. Only slight difference in the octanol-water partition coefficient accompanied this alkylation, suggesting that the increase in permeability is not due to lipophilicity considerations. These observations are, however, consistent with a model in which hydrogen bonding in the backbone is a principal determinant of transport. Methylation is seen to reduce the overall hydrogen bond potential of the peptide and increases flux by this mechanism. These results suggest that alkylation of the amides in the peptide chain is an effective way to improve the passive absorption potential for this class of compounds.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Conradi RA,Hilgers AR,Ho NF,Burton PSdoi
10.1023/a:1015867608405subject
Has Abstractpub_date
1992-03-01 00:00:00pages
435-9issue
3eissn
0724-8741issn
1573-904Xjournal_volume
9pub_type
杂志文章abstract：PURPOSE:To study Cereport (RMP-7, bradykinin B2 agonist) effects on human brain microvascular endothelial cell (HBMEC) monolayer permeability. METHODS:HBMEC grown on transwell membranes were exposed to Cereport. The monolayer permeability was determined with [14C]-inulin (MW. 5,200) and [3H]-dextran (MW. 70,000). RES...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018938722768
更新日期：1999-09-01 00:00:00
abstract：PURPOSE:The aim of the study was to investigate whether dopamine is transferred along the olfactory pathway to the brain following nasal administration to mice. METHODS:[3H]-Dopamine was administered nasally or intravenously to female mice. Brain tissue samples were excised and the radioactive content was measured. Th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007542618378
更新日期：2000-06-01 00:00:00
abstract：PURPOSE:The aim of this study was to investigate whether biodegradable nanocapsules could be obtained by the emulsification-diffusion technique. METHODS:This technique consists of emulsifying an organic solution containing an oil, a polymer, and a drug in an aqueous solution of a stabilizing agent. The subsequent addi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011934328471
更新日期：1998-07-01 00:00:00
abstract：PURPOSE:The purpose of this work was to determine whether a new modeling methodology using fuzzy logic c an predict skin permeability coefficients that are given compound descriptors that have been proven to affect percutaneous penetration. METHOD:Three fuzzy inference models were developed using subtractive clusterin...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1022273115847
更新日期：2003-02-01 00:00:00
abstract：PURPOSE:This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor. METHODS:Plasma samples were collected at 1.5, 4, and 10 h after first oral ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-2765-6
更新日期：2020-01-28 00:00:00
abstract：PURPOSE:To develop novel biomineral-binding liposomes (BBL) for the prevention of orthopedic implant associated osteomyelitis. METHODS:A biomineral-binding lipid, alendronate-tri(ethyleneglycol)-cholesterol conjugate (ALN-TEG-Chol), was synthesized through Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (a versatile...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0812-7
更新日期：2012-11-01 00:00:00
abstract：PURPOSE:The objective of this study was to determine the influence of the peptide bond with emphasis on the carbonyl group on the interaction with and transport by the intestinal small-peptide carrier. Therefore enalapril, a known substrate for the small-peptide carrier, has been modified to an analogue with a reduced ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018866611555
更新日期：1999-01-01 00:00:00
abstract：PURPOSE:The organic cation transporters (OCTs) and multidrug and toxin extrusions (MATEs) together are regarded as an organic cation transport system critical to the disposition and response of many organic cationic drugs. Patient response to the analgesic morphine, a characterized substrate for human OCT1, is highly v...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2526-y
更新日期：2018-10-25 00:00:00
abstract：PURPOSE:1. The assessment of the role of hair follicles and sweat glands in skin resistance and percutaneous iontophoretic flux of 9-desglycinamide, 8-arginine vasopressin (DGAVP) by comparing two skin species: human stratum corneum which contained hair follicles, sweat and sebaceous glands, and shed snake skin which l...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016243706415
更新日期：1995-10-01 00:00:00
abstract：PURPOSE:The aim of this work was to develop PEGylated poly(alkylcyanoacrylate) nanoparticles from a novel methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate copolymer. METHODS:PEGylated and non-PEGylated nanoparticles were formed by nanoprecipitation or by emulsion/solvent evaporation. Nanoparticles si...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011973625803
更新日期：1998-04-01 00:00:00
abstract：:A series of carboxyfluorescein (CF)-containing multilamellar vesicle (MLV) dispersions was prepared and extruded through polycarbonate membranes ranging in size from 0.2 to 5 microns. Vesicle dispersions were nebulized for 80 min using a Collison nebulizer, and the release of CF was monitored during nebulization. Solu...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015896121377
更新日期：1991-02-01 00:00:00
abstract：PURPOSE:To study the biorelevant drug release from novel starch-based polyvinyl alcohol capsules (S-PVA-C). The effect of the shell material is studied by considering microstructural formulation changes during hydration. METHODS:Two different self-emulsifying systems containing either fenofibrate or probucol were fill...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1152-y
更新日期：2014-01-01 00:00:00
abstract：:Colonic absorption of recombinant human insulin-like growth factor I (rhIGF-I) was measured in vitro using both rat and minipig colon. The permeability coefficients were 8.03 +/- 1.03 and 4.75 +/- 0.43 x 10(-8) cm sec-1 in the rat and minipig, respectively. The steady-state flux in rat colon was linearly related to th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018999106684
更新日期：1994-02-01 00:00:00
abstract：:The interaction of dicumarol and phenothiazine neuroleptics binding to alpha 1-acid glycoprotein (AGP) was investigated by circular dichroism (CD) and equilibrium dialysis. The induced CD spectra of the dicumarol-AGP complex were affected differently by the different substituents of the phenothiazine molecule. The sig...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015880327911
更新日期：1992-07-01 00:00:00
abstract：:Photodegradation of solutions of metronidazole in the presence and absence of sodium urate was studied. Photodegradation appeared to follow zero-order kinetics and was found to be dependent on the pH, buffer species, sodium urate concentration, and light source. Complex formation between metronidazole and sodium urate...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015851719579
更新日期：1989-01-01 00:00:00
abstract：PURPOSE:The aim was to design and thoroughly characterize monodisperse Fe3O4@SiO2-Ag nanoparticles with strong antibacterial properties, which makes them a candidate for targeting bacterial infections. METHODS:The monodisperse Fe3O4 nanoparticles were prepared by oleic acid-stabilized thermal decomposition of Fe(III) ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2680-x
更新日期：2019-08-14 00:00:00
abstract：:Liver fibrosis is a pathological condition originating from liver damage that leads to excess accumulation of extracellular matrix (ECM) proteins in the liver. Viral infection, chronic injury, local inflammatory responses and oxidative stress are the major factors contributing to the onset and progression of liver fib...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-014-1497-x
更新日期：2015-02-01 00:00:00
abstract：:Coprecipitates of fluorescein and magnesium hydroxide demonstrate delayed absorption relative to fluorescein solutions when administered to the airways of the isolated perfused rat lung (IPRL). Perfusate concentration vs time profiles showed that dissolution and not epithelial permeability was the rate-controlling fac...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015942013413
更新日期：1988-09-01 00:00:00
abstract：:Excessive production of reactive oxygen species by alveolar macrophages (AMs) in response to inhaled toxic substances is a major cause of oxidative lung injury. Therapeutic approaches designed to protect the lungs from oxidative injury by administering native antioxidant enzymes such as catalase and superoxide dismuta...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018976529766
更新日期：1994-08-01 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:Delivery of therapeutics to neurons is paramount to treat neurological conditions, including many lysosomal storage disorders. However, key aspects of drug-carrier behavior in neurons are relatively unknown: the occurrence of non-canonical endocytic pathways (present in other cells); whether carriers that trave...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1531-z
更新日期：2015-04-01 00:00:00
abstract：PURPOSE:The pharmacokinetics, analgesic efficacy, and irritancy potential of Buprederm, a new transdermal delivery system of buprenorphine, was evaluated. METHODS:Single and multiple dose pharmacokinetic studies were conducted in mice and rabbits. The analgesic efficacy and skin irritation potential were determined by...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9470-6
更新日期：2008-05-01 00:00:00
abstract：PURPOSE:To test the hypothesis that modification of release pattern of nonsteroidal anti-inflammatory drugs (NSAIDs) formulations shifts gastrointestinal (GI) toxicity of the drugs from the upper GI region to the distal intestine. METHODS:We assessed tiaprofenic acid (TA)-induced upper and lower increased GI permeabil...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018887216098
更新日期：1999-01-01 00:00:00
abstract：:This review describes the design and current development of leukotriene biosynthesis inhibitors as potential antiinflammatory agents. Knowledge of the enzymatic mechanism of 5-lipoxygenase led to specific inhibitors of this enzyme which catalyzes a key step in the leukotriene pathway. Competitive inhibitors include ir...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016381215385
更新日期：1985-11-01 00:00:00
abstract：PURPOSE:Propofol is a widely used anesthetic agent with highly desirable fast "on" and "off" effects. It is currently formulated as lipid emulsions, which are known to support microbial growth. In this study, a novel, lipid-free nanodispersion formulation of propofol was characterized. METHODS:The formulation was eval...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-1872-0
更新日期：2005-03-01 00:00:00
abstract：PURPOSE:To characterize the pharmacokinetic/pharmacodynamic (PK/PD) properties of a new polyethylene glycol (PEG) conjugate formulation of interferon (IFN)-beta la following subcutaneous (SC) administration in monkeys. METHODS:Single SC injections of 0.3, 1, and 3 million international units (MIU)/kg of PEG-IFN-beta 1...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-9009-z
更新日期：2005-01-01 00:00:00
abstract：:The role of a bile salt (sodium taurocholate) and lipolysis products (monoglyceride and fatty acid) in the intestinal absorption of a poorly water-soluble drug, diazepam, was investigated. Absorption rates and bioavailabilities were determined with the in situ rat gut technique of Doluisio et al. and analyzing the dia...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016312827680
更新日期：1985-09-01 00:00:00
abstract：PURPOSE:We reported that suramin produced chemosensitization at nontoxic doses. This benefit was lost at the approximately 10-fold higher, maximally tolerated doses (MTD). The aim of the current study was to identify in patients the chemosensitizing suramin dose that delivers 10-50 microM plasma concentrations over 48 ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-0165-1
更新日期：2006-06-01 00:00:00
abstract：PURPOSE:To study the role of unsaturated fatty acid ester substituents in the autoxidation of polysorbate 80 using quantitative kinetics. METHODS:Oxidation kinetics were monitored at 40 degrees C in aqueous solution by tracking head space oxygen consumption using a fiber optic oxygen sensor with phase shift fluorescen...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9946-7
更新日期：2009-10-01 00:00:00
abstract：PURPOSE:Labrasol and Gelucire 44/14 are defined admixtures of acylglycerols and PEG esters which are substrates for digestive lipases. METHODS:We investigated their in vitro gastrointestinal lipolysis to understand which compounds are, after digestion, responsible for keeping poorly water-soluble drugs in solution. Th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9906-2
更新日期：2009-08-01 00:00:00
