Abstract:
:Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Mahato RI,Rolland A,Tomlinson Edoi
10.1023/a:1012187414126subject
Has Abstractpub_date
1997-07-01 00:00:00pages
853-9issue
7eissn
0724-8741issn
1573-904Xjournal_volume
14pub_type
杂志文章,评审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:Herein we report the discovery of a group of derivatized alpha-amino acids that increase the oral bioavailability of sodium cromolyn. METHODS:We prepared three N-acylated alpha-amino acids and used these compounds to demonstrate the oral delivery of cromolyn in an in vivo rat model. In vitro experiments, inclu...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016034913181
更新日期:1996-02-01 00:00:00
abstract:PURPOSE:Indocyanine green (ICG), an FDA-approved near infrared (NIR) dye, has potential application as a contrast agent for tumor detection. Because ICG binds strongly to plasma proteins and exhibits aqueous, photo, and thermal instability, its current applications are largely limited to monitoring blood flow. To addre...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0190-y
更新日期:2010-09-01 00:00:00
abstract::Losartan, an antihypertensive agent in clinical development, was found to exist in two enantiotropic polymorphic forms, a low-temperature stable form (Form I) and a high-temperature stable form (Form II), the temperatures at which they are stable being related to the transition temperature. X-ray powder diffraction pa...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018973530443
更新日期:1993-06-01 00:00:00
abstract::Intraocular enzymes convert the ketoxime analogues of some beta-adrenergic blockers via a sequential bioactivation process involving hydrolysis to the corresponding ketones followed by reduction to the aryloxyaminoalcohols, which then exert known and predictable physiological and pharmacological effects only at the si...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015863521513
更新日期:1990-07-01 00:00:00
abstract::The pharmacokinetics of cefixime, a new orally active cephalosporin, was studied after an intravenous dose of 50 mg/kg to four beagle dogs. Cefixime was shown to exhibit concentration dependent serum protein binding and saturable tubular reabsorption. The drug was excreted mainly in the urine, the net result of glomer...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016309923717
更新日期:1986-06-01 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::The hair follicle, hair shaft, and sebaceous gland collectively form what is recognized as the pilosebaceous unit. This complex, three-dimensional structure within the skin possesses a unique biochemistry, metabolism and immunology. Recent studies have focused on the hair follicle as a potential pathway for both local...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1023/a:1016250422596
更新日期:1995-02-01 00:00:00
abstract::A rapid quantitative, enantioselective HPLC method for the analysis of the four stereoisomers, (+) and (-) erythro and (+) and (-) threo forms, of mefloquine has been developed using a Chiralpak Ad analytical column containing amylose tris-3,5-dimethylphenyl carbonate coated on silica gel and hexane/ethanol/diethylami...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015832912774
更新日期:1992-12-01 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::Antibody drug conjugates (ADCs) are a class of therapeutics that combine the target specificity of an antibody with the potency of a chemotherapeutic. This therapeutic strategy can significantly expand the therapeutic index of a chemotherapeutic by minimizing the systemic exposure and associated toxicity of the chemot...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-012-0800-y
更新日期:2012-09-01 00:00:00
abstract:PURPOSE:The cause of antibody positive pure red cell aplasia associated with the subcutaneous administration of EPREX to patients with chronic kidney failure has been determined to be due to the leaching of weakly adjuvant compounds from the uncoated rubber stoppers that were formerly used in prefilled syringes. Other ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-5356-7
更新日期:2005-07-01 00:00:00
abstract:PURPOSE:Fusogenic liposomes (FLs) are unique delivery vehicles capable of introducing their contents directly into the cytoplasm with the aid of envelope glycoproteins of Sendai virus (SeV). The objective of this study was to evaluate the potential of FL to improve the mucosal absorption of insulin from rat intestinal ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-9175-7
更新日期:2006-02-01 00:00:00
abstract:PURPOSE:To explore the application of scanning ion occlusion sensing (SIOS) as a novel technology for characterization of nanoparticles. METHODS:Liposomes were employed as model nanoparticles. The size distribution of the liposomes was measured by both SIOS and dynamic light scattering (DLS). Particle number concentra...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0788-3
更新日期:2012-09-01 00:00:00
abstract:PURPOSE:Magnetic resonance imaging (MRI) is widely used for diagnostic imaging in preclinical studies and in clinical settings. Considering the intrinsic low sensitivity and poor specificity of standard MRI contrast agents, the enhanced delivery of MRI tracers into tumors is an important challenge to be addressed. This...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1736-9
更新日期:2015-11-01 00:00:00
abstract:PURPOSE:To investigate the effect of atomization conditions on particle size and stability of spray-freeze dried protein. METHODS:Atomization variables were explored for excipient-free (no zinc added) and zinc-complexed bovine serum albumin (BSA). Particle size was measured by laser diffraction light scattering follow...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1007570030368
更新日期:2000-11-01 00:00:00
abstract:PURPOSE:To prepare acylated exenatide analogues and investigate their biological properties for guiding the development of PLGA formulations of exenatide. METHODS:The acylated exenatide analogues were prepared by reaction with glycolic acid (GA), one constitutional unit of PLGA, and characterized by HPLC-MS/MS and Cir...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1298-2
更新日期:2014-08-01 00:00:00
abstract:PURPOSE:Topoisomerase II (Topo II) preferentially cuts DNA at alternating purine-pyrimidine repeats. Different Topo II poisons may affect Topo II to produce distinct drug-specific DNA cleavage patterns. GL331 is a new podophyllotoxin derivative exhibiting potent Topo II-poisoning activity. Therefore, the sequence selec...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011048831698
更新日期:2001-06-01 00:00:00
abstract:PURPOSE:The purpose of the present study was to use the human colorectal carcinoma cell line. Caco-2, as a human intestinal epithelial model for studying the effects of cyclodextrins as absorption enhancers. METHODS:Cyclodextrins of varying sizes and physicochemical characters were investigated. The effects of the cyc...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016225707807
更新日期:1995-09-01 00:00:00
abstract:PURPOSE:The structure-function relationship and mechanism of polycations as gene carriers have attracted considerable research interest in recent years. The present study was to investigate the relationship between polycation chain length and transfection efficiency (RCL-TE), and the corresponding mechanism by O-methyl...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1211-4
更新日期:2014-04-01 00:00:00
abstract::The pharmacokinetics of trilostane and one of its metabolites ketotrilostane are described and characterized in the rat following the separate intravenous administration of trilostane and ketotrilostane. It was noted during these studies that the parent compound and its metabolite undergo metabolic interconversion-tri...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015828027060
更新日期:1992-04-01 00:00:00
abstract::The interaction between several marker solutes and a polyolefin laminate polymer was studied in several solutions. Solutions studied included mixtures of sodium chloride and dextrose (at concentrations more less typical of i.v. administration solutions) and several actual i.v. products [lactated Ringer's injection, Di...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015866420836
更新日期:1991-06-01 00:00:00
abstract:PURPOSE:Targeted delivery of aerosols could not only improve efficacy of inhaled drugs but also reduce side effects resulting from their accumulation in healthy tissue. Here we investigated the impact of magnetized aerosols on model drug accumulation and transgene expression in magnetically targeted lung regions of una...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0682-z
更新日期:2012-05-01 00:00:00
abstract:OBJECTIVE:Amorphous pharmaceuticals, a viable approach to enhancing bioavailability, must be stable against crystallization. An amorphous drug can be stabilized by dispersing it in a polymer matrix. To implement this approach, it is desirable to know the drug's solubility in the chosen polymer, which defines the maxima...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9784-z
更新日期:2009-04-01 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::A new method of analysis for the antihypertensive drug, hydralazine, is introduced. The assay involves the addition of p-nitrobenzaldehyde to blood samples containing hydralazine, to form a stable Schiff's base, hydralazine p-nitrobenzaldehyde hydrazone. The derivative is extracted from the blood into hexane and the s...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015915812987
更新日期:1988-06-01 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::Chimeric L6 is a mouse-human monoclonal antibody specific for tumor cell-associated antigens. The factors affecting the physical and chemical stability of chimeric L6 were assessed at elevated temperatures (30-60 degrees C) and by multiple freezing and thawing. Three routes of degradation were observed: chemical degra...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018948901599
更新日期:1994-05-01 00:00:00
abstract:PURPOSE:Previously, we have shown that complexes of plasmid DNA with the biodegradable polymer poly(2-dimethylamino ethylamino)phosphazene (p(DMAEA)-ppz) mediated tumor selective gene expression after intravenous administration in mice. In this study, we investigated the effect of p(DMAEA)-ppz molecular weight on both ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9299-z
更新日期:2007-08-01 00:00:00
abstract::A sensitive activity assay for high volume evaluation of human renin inhibitory peptides (RIPs) in rat sera (range 2-80 ng/ml) was developed based on the low affinity of RIPs to rat renin and their high affinity to human renin. The utility of this activity assay was tested by measuring concentrations of a human RIP, U...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015883709275
更新日期:1990-04-01 00:00:00