Abstract:
:Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells, and sustained maintenance of the viral genome. However, several problems should be addressed to enhance the utility of AAV vectors, particularly those based on AAV2, the best characterized AAV serotype. First, altering viral tropism would be advantageous for broadening its utility in various tissue or cell types. In response to this need, vector pseudotyping, mosaic capsids, and targeting ligand insertion into the capsid have shown promise for altering AAV specificity. In addition, library selection and directed evolution have recently emerged as promising approaches to modulate AAV tropism despite limited knowledge of viral structure-function relationships. Second, pre-existing immunity to AAV must be addressed for successful clinical application of AAV vectors. "Shielding" polymers, site-directed mutagenesis, and alternative AAV serotypes have shown success in avoiding immune neutralization. Furthermore, directed evolution of the AAV capsid is a high throughput approach that has yielded vectors with substantial resistance to neutralizing antibodies. Molecular engineering and directed evolution of AAV vectors therefore offer promise for generating 'designer' gene delivery vectors with enhanced properties.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Kwon I,Schaffer DVdoi
10.1007/s11095-007-9431-0subject
Has Abstractpub_date
2008-03-01 00:00:00pages
489-99issue
3eissn
0724-8741issn
1573-904Xjournal_volume
25pub_type
杂志文章,评审abstract:PURPOSE:LY3015014 is a humanized immunoglobulin G4 (IgG4) monoclonal antibody that binds to the catalytic domain of PCSK9 and reduce low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia that is poorly controlled by maximally tolerated statin therapy. The objective of this pharmacokinetic/ph...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-2054-6
更新日期:2017-01-01 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:β-Hydroxy-β-methylbutyrate (HMB), a nutritional supplement, elicits anabolic activity in muscle. Here we investigated the mechanism of HMB uptake in muscle cells. METHODS:Murine muscle cells (C2C12) and human mammary epithelial cells (MCF7) were used for uptake. As HMB is a monocarboxylate, focus was on monoca...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2626-3
更新日期:2019-04-17 00:00:00
abstract:PURPOSE:The objective of this study was to elucidate the different mechanisms of action of different excipients on the oxidation of Met1, Met122, Met127, and Met138 in granulocyte colony-stimulating factor (G-CSF) by using hydrogen peroxide as the oxidant. METHODS:The oxidation of Met1, Met127, and Met138 was quantifi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-004-9019-x
更新日期:2005-01-01 00:00:00
abstract:PURPOSE:The objective of the current study was to investigate whether blood-brain barrier (BBB) permeability studies in vitro could be accelerated by running several compounds together in the same experiment. METHODS:To address this question, we compared the transport of six compounds run separately with the results o...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000026424.78528.11
更新日期:2004-05-01 00:00:00
abstract:PURPOSE:To characterize the uptake mechanism of zidovudine (AZT), a nucleoside reverse transcriptase inhibitor, in syncytiotrophoblast cells using the TR-TBT 18d-1 cell line previously established by our group. MATERIALS AND METHODS:The effects of several transporter inhibitors on the initial and steady-state apical u...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9564-9
更新日期:2008-07-01 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:To prepare a thermoreversible gel system able to work as a medium for crystallization at around 20°C, allowing easy retrieval of crystals by simply decreasing the gel temperature. Lactose was selected has model substance for crystallization. METHODS:Water solutions with different% of poloxamer 407, α-Lactose m...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0606-3
更新日期:2012-03-01 00:00:00
abstract:PURPOSE:Exenatide, a potent insulinotropic agent, can be used for the treatment of non-insulin-dependent diabetes mellitus. However, the need for frequent injections seriously limits its therapeutic utility. The aim of present report was to develop an orally available exenatide formulation using goblet cell-targeting n...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1513-1
更新日期:2015-03-01 00:00:00
abstract:PURPOSE:Preparation of Nanographene oxide (NGO) - Gelatin hybrids for efficient treatment of Neuroblastoma. METHODS:Nanohybrids were prepared via non-covalent interactions. Spectroscopic tools have been used to discriminate the chemical states of NGO prior and after gelatin coating, with UV visible spectroscopy reveal...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1604-z
更新日期:2015-06-01 00:00:00
abstract:PURPOSE:The purpose of this research was to evaluate the effect of ultrasound on mass transport across fetal membrane for direct fetal drug delivery and sensing of the amniotic fluid in a noninvasive manner. METHODS:Post-delivery human fetal membranes (chorioamnion) were used for in vitro experiments, in which the eff...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1470-8
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::Short-lived gamma emitting radioisotopes can be incorporated into polylactide/glycolide polymeric microspheres with various specific activities for possible use in understanding the in-vivo deposition, distribution and clearance of microparticulate drug carrier systems. The incorporated radiolabel is stable with negli...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016237216352
更新日期:1995-12-01 00:00:00
abstract::A reverse-phase HPLC method for the analysis of tryptic digests of recombinant porcine growth hormone (pGH) has been developed and validated. Digestion was performed at 4 degrees C for a 20-hr period with TPCK-treated trypsin at a 1:20 (w/w) trypsin:pGH ratio. Gradient elution HPLC, using an Aquapore RP300 C8 column, ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018927426268
更新日期:1993-10-01 00:00:00
abstract:PURPOSE:The amphiphilic block copolymer Pluronic P85 (P85) increases the permeability of the blood-brain barrier (BBB) with respect to a broad spectrum of drugs by inhibiting the drug efflux transporter, P-glycoprotein (Pgp). In this regard, P85 serves as a promising component for CNS drug delivery systems. To assess t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000048189.79606.6e
更新日期:2004-11-01 00:00:00
abstract::The pharmacokinetics of Sb was examined in 29 patients with cutaneous leishmaniasis following the intramuscular administration of a dose of sodium stibogluconate equivalent to 600 mg of Sb. Blood was sampled at different time intervals from each patient and Sb was measured in whole blood by electrothermal atomic absor...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016251023427
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:Reverse micellar solutions of diclofenac sodium were encapsulated in soft gelatine capsules. On contact with aqueous media they exhibited an application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) which slows down drug release. The aim of the present paper was to study in vitr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012127829032
更新日期:1997-12-01 00:00:00
abstract:PURPOSE:Due to protease inhibitor (PI) efflux transport by P-glycoprotein (P-gp), insufficient PI concentrations result in low ongoing HIV replication in the so-called virus sanctuaries (brain and testes). The aim of the present study was to evaluate indinavir-loaded nanocapsules (Ind-LNC) including Solutol HS15, an ex...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-7147-6
更新日期:2005-11-01 00:00:00
abstract:PURPOSE:To investigate the suitability of three antimicrobial peptides (AMPs) as cell-penetrating antimicrobial peptides. METHODS:Cellular uptake of three AMPs (PK-12-KKP, SA-3 and TPk) and a cell-penetrating peptide (penetratin), all 5(6)-carboxytetramethylrhodamine-labeled, were tested in HeLa WT cells and analyzed ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1550-9
更新日期:2015-05-01 00:00:00
abstract:PURPOSE:Simvastatin (SIM), a HMG-CoA reductase inhibitor widely prescribed for hypercholesterolemia, has been reported to ameliorate inflammation and promote osteogenesis. Its clinical applications on these potential secondary indications, however, have been hampered by its lack of osteotropicity and poor water solubil...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2444-z
更新日期:2018-06-25 00:00:00
abstract:PURPOSE:To improve the delivery of liposomes to tumors using P-selectin glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are upregulated on tumorassociated endothelium. METHODS:PSGL1 was orientated and presented on the surface of liposomes to achieve optimal selectin binding using a novel st...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0875-5
更新日期:2013-02-01 00:00:00
abstract:PURPOSE:An in vitro dynamic pharmacokinetic (PK) cell culture system was developed to more precisely simulate physiologic nanoparticle/drug exposure. METHODS:A dynamic PK cell culture system was developed to more closely reflect physiologic nanoparticle/drug concentrations that are changing with time. Macrophages were...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2576-9
更新日期:2019-02-01 00:00:00
abstract:PURPOSE:To study the influence of cytotoxicity of macromolecules, VEGF gene expression, and vascular permeability on the enhanced permeability and retention (EPR) effect. METHODS:Mice bearing xenografts of A2780 multidrug resistant human ovarian carcinoma were treated by free doxorubicin (DOX) and N-(2-hydroxypropyl)m...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1007500412442
更新日期:2000-05-01 00:00:00
abstract:PURPOSE:E-selectin is a cell adhesion molecule that is specifically expressed in the inflammatory vascular endothelium in response to cytokines such as IL-1 beta and TNF-alpha, and interacts with specific ligands containing sialyl Lewis X (Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-, SLex). In order to investiga...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018849029727
更新日期:1999-02-01 00:00:00
abstract::Microbial metabolism studies of the antimalarial drug arteether (1) have shown that arteether is metabolized by a number of microorganisms. Large-scale fermentation with Aspergillus niger (ATCC 10549) and Nocardia corallina (ATCC 19070) have resulted in the isolation of four microbial metabolites which have been chara...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015845306124
更新日期:1990-02-01 00:00:00
abstract:PURPOSE:To study the expression of P-glycoprotein (P-gp), lung resistance-related protein (LRP), and caveolin-1 (cav-1) in the human bronchial epithelial cell line 16HBE14o-. METHODS:The presence of P-gp, LRP, and cav-1 in 16HBE14o- cell layers was evaluated using immunocytochemical staining and visualization with con...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1023230328687
更新日期:2003-04-01 00:00:00
abstract:PURPOSE:This study was conducted to investigate the cause of incomplete protein release from photopolymerized poly(ethylene glycol) (PEG) hydrogels and verify the protein-protection mechanism provided by iminodiacetic acid (IDA). METHODS:The in vitro release of bovine serum albumin (BSA) from PEG hydrogels prepared un...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-9395-x
更新日期:2006-03-01 00:00:00
abstract:PURPOSE:To characterize the electrochemical behavior of the photodegradation product of nifedipine, i.e., 2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridine-carboxylic acid dimethyl ester (NPD) in different electrolytic media. We also evaluated the interaction between free radicals generated from NPD and xeno/endobiotics. ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015112216360
更新日期:2002-04-01 00:00:00
abstract:PURPOSE:The aim of the study is to determine whether a biodegradable elastomeric device that uses an osmotic pressure delivery mechanism can release different therapeutic proteins at a nearly constant rate in nanomolar concentrations with high bioactivity, given the same formulation conditions. Vascular endothelial gro...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9750-6
更新日期:2006-04-01 00:00:00
abstract:PURPOSE:Simple uncoated compressed tablets with a central hole (donut-shape) are proposed to provide a constant drug release over a long period of time (> 20 hrs). The effect of hole size and drug solubility on the release kinetics is investigated. METHODS:The donut-shaped polyethylene oxide (PEO, Mw = 4 x 10(6)) tabl...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016218716951
更新日期:1995-07-01 00:00:00