Abstract:
PURPOSE:This study compared gene expression profiles in mouse lungs after administration of the cationic polymers polyethyleneimine (PEI) or chitosan alone or formulated with a luciferase reporter plasmid (PEI-pLuc, chitosan-pLuc). METHODS:The polymers and formulations were administered intratracheally to Balb/c mice at doses judged to be nontoxic according to intracellular dehydrogenase activity and tissue morphology. RNA was isolated from the lungs 24 or 72 h after administration, and a dedicated stress and toxicology cDNA array was used to monitor the in vivo response to the gene delivery system in the lung tissue. RESULTS:The gene expression profiles differed between the PEI and chitosan groups with regard to both the total number and the type of expressed genes. Chitosan-pLuc upregulated genes that protect the cell from oxidative stress and inflammation, such as heme oxygenase-1 and catalase, whereas PEI-pLuc upregulated genes involved in inflammatory processes, such as the cyclooxygenases 1 and 2, indicating possible involvement in the development of adverse reactions. However, both polymers activated genes involved in reaction to stress, such as DNA damage repair. Furthermore, in the PEI group, chaperone genes and members of the p38 mitogen-activated protein kinase pathway were also upregulated, suggesting a possible explanation for the better performance of PEI in gene delivery systems. CONCLUSIONS:The results indicate that gene expression profiling is a useful and sensitive tool for the evaluation of tissue responses after administration of polymers or gene delivery systems. The results also suggest a possible explanation for the differences in gene delivery performance between the two polymers in gene delivery systems.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Regnström K,Ragnarsson EG,Fryknäs M,Köping-Höggård M,Artursson Pdoi
10.1007/s11095-006-9563-7subject
Has Abstractpub_date
2006-03-01 00:00:00pages
475-82issue
3eissn
0724-8741issn
1573-904Xjournal_volume
23pub_type
杂志文章abstract:PURPOSE:The heparin-paclitaxel conjugates using amino acid as linker (HD2), with low anticoagulant activity, the similar anticancer activity as paclitaxel, offer great potential for further investigation. METHODS:Two types of heparin-paclitaxel conjugates (HD) have been developed, in which O-acetylated heparin as carr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9762-5
更新日期:2009-04-01 00:00:00
abstract:PURPOSE:To evaluate the use of an in vitro intestinal permeability model to predict rat and human absorption as well as to evaluate the use of an internal standard to control for intra- and inter-rat variability. METHODS:In vivo peroral absorption and in vitro steady-state intestinal permeability coefficients were det...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012148300807
更新日期:1997-12-01 00:00:00
abstract::In this study the intestinal degradation and absorption of a synthetic pentapeptide, metkephamid, were investigated in the rat by determination of its wall permeabilities in the small and large intestine and the extent and mechanism of its intestinal degradation. The peptide was metabolized in the gut wall through con...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018962415287
更新日期:1994-04-01 00:00:00
abstract::The transport of thyrotropin releasing hormone (TRH) in rabbit buccal mucosa in vitro has been investigated with respect to (a) rate and type of metabolism of TRH on mucosal and serosal sides of buccal mucosa, (b) mechanism of TRH transport including charge effect on its permeability, and (c) pathway and rate-limiting...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015883217858
更新日期:1992-09-01 00:00:00
abstract:PURPOSE:To design and synthesize fatty acid-RGD peptide amphiphiles with ADA linker for their potential delivery of hydrophobic drugs like paclitaxel targeted to α(v)β(3) integrin overexpressing tumors. METHODS:Four amphiphiles - C16 or C18 fatty acid-RGD peptide and ADA linker were designed and synthesized. CMC, size...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0830-5
更新日期:2012-12-01 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:PURPOSE:To evaluate organic anion transporter-mediated drug-drug interaction (DDI) potential for individual active components of Danshen (Salvia miltiorrhiza) vs. combinations using in vitro and in silico approaches. METHODS:Inhibition profiles for single Danshen components and combinations were generated in stably-ex...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1437-9
更新日期:2014-12-01 00:00:00
abstract:PURPOSE:The fate of inhaled salmon calcitonin (sCT) at the respiratory epithelial barrier was studied with particular emphasis on enzymatic degradation by trypsin, chymotrypsin, and neutrophil elastase. METHODS:Degradation of sCT was assessed by HPLC in cell homogenate, supernatant and intact monolayers of human respi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0553-z
更新日期:2012-01-01 00:00:00
abstract::This study utilized different statistical techniques to evaluate the reliability (internal consistency) and the discriminant validity of the most widely used measures of organizational commitment and intention to quit (the employing organization). Data were obtained from a national mail survey of members of the Americ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018930718979
更新日期:1994-01-01 00:00:00
abstract::A number of substituted phthalimide, 1, 8-naphthalimide, succinimide and glutarimide derivatives demonstrated significant hypolipidemic activity at 20 mg/kg/ day, I.P. after 16 days dosing. The N-(n-pentyl) succinimide proved to be the most potent analogue of the new compounds, lowering serum triglyceride levels 51 % ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016346018962
更新日期:1984-11-01 00:00:00
abstract:PURPOSE:To investigate the ability of various polymers to inhibit the crystallization of amorphous felodipine from amorphous molecular dispersions in the presence of absorbed moisture. METHODS:Spin coated films of felodipine with poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9331-3
更新日期:2008-04-01 00:00:00
abstract::The intrasubject and intersubject variabilities for CGS 16617, an angiotensin converting enzyme inhibitor, were evaluated in an open-label, repeat single-dose bioavailability trial. Eight healthy male volunteers each received a 20-mg oral dose of CGS 16617 as an aqueous solution on four separate occasions. Components ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015954609527
更新日期:1989-04-01 00:00:00
abstract::Seven healthy, male volunteers were entered into a randomized, open crossover study of the gastrointestinal transit of two enteric-coated 500-mg naproxen tablets. Two radiolabeled tablets were given to each volunteer on two occasions separated by 7 days, once in the fasted state and once after breakfast. Radiolabeling...
journal_title:Pharmaceutical research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1015858829187
更新日期:1992-11-01 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 develop a statistical model for predicting effect of food on the extent of absorption (area under the curve of time-plasma concentration profile, AUC) of drugs based on physicochemical properties. MATERIALS AND METHODS:Logistic regression was applied to establish the relationship between the effect of food ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9236-1
更新日期:2007-06-01 00:00:00
abstract:PURPOSE:The sensitivity and effectiveness of indirect metrics proposed for the assessment of comparative absorption rates in bioequivalence studies [Cmax, Tmax, partial AUC (AUCp), feathered slope (SLf), intercept metric (I)] were originally tested by assuming first-order absorption. The present study re-evaluates thei...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1007521016985
更新日期:2000-05-01 00:00:00
abstract:PURPOSE:The objective of this study was to compare two different nebulizers: Eflow rapid® and Pari LC star® by scintigraphy and PK modeling to simulate epithelial lining fluid concentrations from measured plasma concentrations, after nebulization of CMS in baboons. METHODS:Three baboons received CMS by IV infusion and...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1716-0
更新日期:2015-10-01 00:00:00
abstract:PURPOSE:Comparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions. METHODS:Dissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering....
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2233-0
更新日期:2017-11-01 00:00:00
abstract:PURPOSE:It is reported that the cerebrospinal fluid (CSF) to plasma unbound concentration ratio of fleroxacin at steady-state is approximately 0.5 in experimental animals. These results can be accounted for by assuming the presence of an active transport system for the efflux of this compound across the choroid plexus....
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016081618149
更新日期:1996-04-01 00:00:00
abstract:PURPOSE:Vancomycin (VCM) concentration is often out of therapeutic range (10-20 μg/ml) in patients receiving continuous renal replacement therapy (CRRT). The purposes of this study were to develop a practical VCM population pharmacokinetic (PPK) model and to evaluate the potential of Bayesian prediction-based therapeut...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02820-0
更新日期:2020-05-28 00:00:00
abstract:PURPOSE:Because interleukin-10 (IL-10) seems a promising new antifibrotic drug, we investigated the pharmacokinetic and biodistribution profile of this potent therapeutic cytokine in rats with extensive liver fibrosis (BDL-3). IL-10 receptor expression was also determined in relation to these aspects. METHODS:To study...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000048199.94510.b0
更新日期:2004-11-01 00:00:00
abstract:PURPOSE:The acne skin is characteristic of a relatively lower pH microenvironment compared to the healthy skin. The aim of this work was to utilize such pH discrepancy as a site-specific trigger for on-demand topical adapalene delivery. METHODS:The anti-acne agent, adapalene, was encapsulated in acid-responsive polyme...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1398-z
更新日期:2014-11-01 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
pub_type: 杂志文章
doi:10.1007/s11095-018-2378-5
更新日期:2018-03-19 00:00:00
abstract:PURPOSE:This study was conducted to investigate in vivo the impact of interferon-alpha (IFN)-alpha on P-glycoprotein (P-gp) activity in rats by studying how its administration modifies the bioavailability of digoxin, a fairly pure P-gp substrate. METHODS:Human recombinant IFN-alpha was given to rats (n = 5-7 per group...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-7415-5
更新日期:2005-11-01 00:00:00
abstract:PURPOSE:Interferon beta is commonly used as therapeutic in the first line of therapy for multiple sclerosis. However, depending on the product, it induces an antibody response in up to 60% of patients. This study evaluated the impact of therapy related factors like dose, route of administration and administration frequ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-0992-9
更新日期:2013-06-01 00:00:00
abstract::Semitelechelic poly[N-(2-hydroxypropyl)methacrylamide]s (ST-PHPMA) containing one amino end-group and differing in molecular weight were synthesized by radical polymerization in the presence of 2-aminoethanethiol (AET) as chain transfer agent. These polymers were covalently attached via amide bonds to the surface of n...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016247206531
更新日期:1995-05-01 00:00:00
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 methy...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015867608405
更新日期:1992-03-01 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::The dermal route is an attractive route for vaccine delivery due to the easy skin accessibility and a dense network of immune cells in the skin. The development of microneedles is crucial to take advantage of the skin immunization and simultaneously to overcome problems related to vaccination by conventional needles (...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-017-2223-2
更新日期:2017-11-01 00:00:00
abstract:PURPOSE:We investigated optimum formulation characteristics in the nasal absorption of salmon calcitonin (sCT) by incorporation of acylcarnitines. METHODS:Nasal sCT formulations were administered to anesthetized rats. Plasma calcium level was measured and pharmacological bioavailability (P.bioav) was calculated. RESU...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016051600828
更新日期:1996-05-01 00:00:00