Abstract：
:Nanoparticles, including lipopolyamines leading to lipoplexes, liposomes, and polyplexes are targeted drug carrier systems in the current search for a successful delivery system for polynucleic acids. This review is focused on the impact of gene and siRNA delivery for studies of efficacy, pharmacodynamics, and pharmacokinetics within the setting of the wide variety of in vivo animal models now used. This critical appraisal of the recent literature sets out the different models that are currently being investigated to bridge from studies in cell lines through towards clinical reality. Whilst many scientists will be familiar with rodent (murine, fecine, cricetine, and musteline) models, few probably think of fish as a clinically relevant animal model, but zebrafish, madake, and rainbow trout are all being used. Larger animal models include rabbit, cat, dog, and cow. Pig is used both for the prevention of foot-and-mouth disease and human diseases, sheep is a model for corneal transplantation, and the horse naturally develops arthritis. Non-human primate models (macaque, common marmoset, owl monkey) are used for preclinical gene vector safety and efficacy trials to bridge the gap prior to clinical studies. We aim for the safe development of clinically effective delivery systems for DNA and RNAi technologies.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Blagbrough IS,Zara Cdoi
10.1007/s11095-008-9646-8subject
Has Abstractpub_date
2009-01-01 00:00:00pages
1-18issue
1eissn
0724-8741issn
1573-904Xjournal_volume
26pub_type
杂志文章,评审abstract：PURPOSE:To develop a dose dependent version of BCS and identify a critical dose after which the amount absorbed is independent from the dose. METHODS:We utilized a mathematical model of drug absorption in order to produce simulations of the fraction of dose absorbed (F) and the amount absorbed as function of the dose ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0815-4
更新日期：2012-11-01 00:00:00
abstract：:Various carboxylic acid esters of the N-hydroxymethyl derivative of N-benzyloxycarbonylglycine benzylamide, used as a peptide-like model, were prepared and their decomposition kinetics studied in aqueous solution and in human plasma solutions. These N-acyloxymethylamide derivatives were found to undergo a facile decom...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015839426229
更新日期：1991-10-01 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 aim was to investigate the influence of polymer content and molecular weight on the morphology and heat- and moisture-induced transformations, as indicators of stability, of spray-dried composite particles of amorphous lactose and poly(vinylpyrrolidone) (PVP). METHODS:Amorphous lactose and composite partic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1024462306941
更新日期：2003-07-01 00:00:00
abstract：PURPOSE:Pulmonary antibiotic delivery is recommended as maintenance therapy for cystic fibrosis (CF) patients who experience chronic infections. However, abnormally thick and sticky mucus present in the respiratory tract of CF patients impairs mucus penetration and limits the efficacy of inhaled antibiotics. To overcom...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1921-5
更新日期：2016-08-01 00:00:00
abstract：PURPOSE AND METHODS:Data from 358 pharmacist-patient encounters in 12 community pharmacies were used to investigate the association of prescription status, patient age, patient gender, and patient question asking with the content of pharmacist-patient communication. RESULTS:There was an association between prescriptio...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012084207399
更新日期：1997-02-01 00:00:00
abstract：:The synthesis of an homologous series of new water-soluble derivatives of pilocarpine is described. The new compounds, referred to as soft quaternary salts, are water soluble by virtue of a cationic ammonium head and their lipophilicity can be modulated by manipulating the size and the nature of the substituent in the...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015847103862
更新日期：1992-03-01 00:00:00
abstract：:Monte Carlo simulation technique used to evaluate the effect of the arrangement of concentrations on the efficiency of estimation of population pharmacokinetic parameters in the preclinical setting is described. Although the simulations were restricted to the one compartment model with intravenous bolus input, they pr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016267811074
更新日期：1995-05-01 00:00:00
abstract：PURPOSE:Highly lipophilic basic drugs, the antiestrogens AE 1 (log P = 5.82) and AE 2 (log P = 7.8) shall be delivered transdermally. METHODS:Transdermal permeation of drugs, enhancers, and solvents from various fluid formulations were characterized by in-vitro permeation studies through excised skin of hairless mice....
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015314314796
更新日期：2002-05-01 00:00:00
abstract：PURPOSE:Locoregional recurrence is the most common complication after adenocarcinoma resection in the colon, despite adjuvant chemotherapy. Therapy efficacy could be improved if designed to target malignant cells by incorporating specific recognition factors in the drugs or the drug vehicles. The aim of this study was ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9330-4
更新日期：2008-02-01 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 investigate the effect of tyrphostin 8 (T-8), a GTPase inhibitor, on transferrin receptor (TfR)-mediated transcytosis of insulin-transferrin (In-Tf) conjugate in cultured enterocyte-like Caco-2 cells and on gastrointestinal (GI) absorption of In-Tf in streptozotocin (STZ)-induced diabetic rats. METHODS:Caco...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011032502097
更新日期：2001-02-01 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：:Molecular modeling has been used to study the complexation between alpha, beta, or gamma-cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. The computer program SYBYL 5.3 and the Tripos force field (version 5.2) were used for all the calculations. Three-dimensional structures of ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015816215751
更新日期：1991-10-01 00:00:00
abstract：PURPOSE:Induction of cell-mediated immune (CMI) responses is crucial for vaccine-mediated protection against difficult vaccine targets, e.g., Chlamydia trachomatis (Ct). Adjuvants are included in subunit vaccines to potentiate immune responses, but many marketed adjuvants stimulate predominantly humoral immune response...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2180-9
更新日期：2017-08-01 00:00:00
abstract：PURPOSE:Long-acting injectables (LAIs) are increasingly recognized as an effective therapeutic approach for treating chronic conditions. Many LAIs are formulated to create a poorly soluble depot from which the active agent is delivered over time. This long residing depot can cause localized chronic-active inflammation ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1308-4
更新日期：2014-08-01 00:00:00
abstract：PURPOSE:[corrected] The purpose of this study was to design novel gastroretentive dosage forms (GRDFs) based on unfolding multilayer polymeric films, to investigate the mechanism of their gastroretentivity in dogs, and to assess the effect of compounding a narrow absorption window drug in a GRDF on the drug's absorptio...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020412817716
更新日期：2002-10-01 00:00:00
abstract：PURPOSE:In this study, modulation of the immune response against diphtheria toxoid (DT) by various adjuvants in transcutaneous immunization (TCI) with microneedle array pretreatment was investigated. METHODS:TCI was performed on BALB/c mice with or without microneedle array pretreatment using DT as a model antigen co-...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9874-6
更新日期：2009-07-01 00:00:00
abstract：:A new high-performance liquid chromatographic (HPLC) assay suitable for pharmacokinetic studies of enantiomers of fenoprofen (FEN) was developed. Following the addition of internal standard (IS; racemic ketoprofen), the plasma or urine constituents are extracted into a mixture of isooctane:isopropanol (95:5), back ext...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015867513045
更新日期：1988-01-01 00:00:00
abstract：:Since ancient times, natural products, herbs and spices have been used for preventing several diseases, including cancer. The term chemoprevention was coined in the late 1970s and referred to the prevention of cancer by selective use of phytochemicals or their analogs. The field utilizes experimental carcinogenesis mo...
journal_title：Pharmaceutical research
pub_type： 历史文章,杂志文章,评审
doi：10.1007/s11095-010-0085-y
更新日期：2010-06-01 00:00:00
abstract：:The physicochemical properties and crystal structures of the crystalline salts formed by the interaction of an achiral anion, salicylate, with homochiral and racemic ephedrinium and pseudoephedrinium cations were determined. The interaction of ephedrinium or pseudoephedrinium with salicylate in aqueous solution yielde...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018945401484
更新日期：1994-11-01 00:00:00
abstract：:The influence of varying protein and fat content in milk of New Zealand White rabbits on the milk-to-plasma drug concentration (M/P) ratio of diazepam was studied. At various time points after littering, a bolus dose (1.5 mg/kg) followed by a 26-hr infusion (1.8 mg/h) of diazepam was administered to freely moving rabb...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015809418284
更新日期：1992-10-01 00:00:00
abstract：PURPOSE:One of the drawbacks of polycationic and cationic liposomal gene transfer is its sensitivity to serum. Gene therapy requires the transfectant-DNA complex to be resistant to serum as well as blood. Since Ca2+ has proved to be an efficient cofactor of polycationic gene transfer, we decided to investigate its effe...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007581700996
更新日期：2000-02-01 00:00:00
abstract：PURPOSE:Solid lipid nanoparticles (SLNs) have been proposed as a colloidal carrier system that could enhance the oral bioavailability of curcumin. However, a burst release of the loaded drug, which occurs in acidic environments, has been a main obstacle to the oral delivery of curcumin by using SLNs as a carrier system...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1469-1
更新日期：2015-02-01 00:00:00
abstract：PURPOSE:Since the absorption of ceftriaxone (CTO) in the intestine is restricted by its natural physiological characteristics, we developed a series of small synthetic compounds derived from bile acids to promote the absorption of CTO in the gastrointestinal tract. METHODS:Several bile acid derivatives were screened b...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0932-0
更新日期：2013-04-01 00:00:00
abstract：PURPOSE:To apply physiologically-based pharmacokinetic (PBPK) modeling to investigate the consequences of reduction in activity of hepatic and intestinal uptake and efflux transporters by cyclosporine and its metabolite AM1. METHODS:Inhibitory potencies of cyclosporine and AM1 against OATP1B1, OATP1B3 and OATP2B1 were...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0918-y
更新日期：2013-03-01 00:00:00
abstract：PURPOSE:To determine the pharmacokinetics of GS-522, an oligodeoxynucleotide (GGTTGGTGTGGTTGG) inhibitor of thrombin, after constant infusion and bolus administration in the cynomolgus monkey. METHODS:Using a stability indicating HPLC method, the GS-522 plasma concentration versus time data were obtained after constan...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016295907266
更新日期：1995-12-01 00:00:00
abstract：PURPOSE:To elucidate the catalytic mechanism of the esterase-like activity of serum albumin (SA), the reactivity of SA from six species was investigated using p-nitrophenyl esters as model substrates. METHODS:The effect of pH and the energetic and thermodynamic profiles of SA were determined for all species for p-nitr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000016241.84630.06
更新日期：2004-02-01 00:00:00
abstract：PURPOSE:To develop an isolated perfused rat liver (IPRL) model with low baseline levels of tumor necrosis factor (TNF)-alpha in the outlet perfusate to study the effects of immunostimulants and immunosuppressants on the release of TNF-alpha from this organ. METHODS:Isolated rat livers were perfused with a buffer conta...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013603331899
更新日期：2002-01-01 00:00:00
abstract：PURPOSE:Orally absorbable anticancer medications have great advantages for conventional cancer therapies to patients. Here we evaluated the potent anticancer effect of orally absorbable LHD, a chemical conjugate of low-molecular-weight heparin and deoxycholic acid, on tumor graft growth models. METHODS:We characterize...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9989-9
更新日期：2009-12-01 00:00:00
