Abstract:
BACKGROUND:The polycationic nanopeptide RKKRRQRRR is a fragment of HIV-Tat protein known to be a transfection enhancer. Such factors control the transfection efficiency of plasmid DNA complexed with tat peptide. However, their actions are poorly understood. METHODS AND RESULTS:Several cell lines and primary cells were used in transfection experiments. The optimal charge ratio of plasmid to the branched 8Tat peptide was 1:8 for all cell lines and primary cells tested except primary human skin fibroblasts where it was 1:4. The conditions of complex formation (volume, DNA-peptide-solution mixing order and the nature of solution (HEPES, 0.15 M NaCl or 5% dextrose)) influenced transfection efficiency. Chloroquine increased the transgene expression 50-fold in HeLa cells but had little impact on Cos7 cells or 3T3 fibroblasts. The integrity of plasmid DNA in the presence of DNase I was shown to be dependent on the DNA/Tat ratio and the nature of the complex solvent. Complexes with -/+ charge ratio of 1:8 formulated in NaCl and dextrose provided high degree of DNA resistance towards nuclease degradation. CONCLUSIONS:The conditions of DNA-peptide complex formation and DNA/Tat ratio have significant impact on the level of transgene expression and degree of DNA protection from nuclease attack. The level of elevation of gene delivery in the presence of chloroquine varied considerably between different cells, indicating possible different mechanisms of plasmid-peptide internalisation and intracellular trafficking. The efficiency of branched 8Tat peptide as a plasmid DNA carrier varied between different cell types and have to be optimised for each application.
journal_name
J Drug Targetjournal_title
Journal of drug targetingauthors
Hellgren I,Gorman J,Sylvén Cdoi
10.1080/106118604200041403keywords:
subject
Has Abstractpub_date
2004-01-01 00:00:00pages
39-47issue
1eissn
1061-186Xissn
1029-2330pii
3PNR6Q39PA4EUBVNjournal_volume
12pub_type
杂志文章abstract::The ability of a polymer therapeutic to access the appropriate subcellular location is crucial to its efficacy and is defined to a large part by the many and complex cellular biological and biochemical barriers such that a construct must traverse. It is shown here that model dextrin conjugates are able to pass through...
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abstract::The aim of this work was to formulate minoxidil loaded liposome and niosome formulations to improve skin drug delivery. Multilamellar liposomes were prepared using soy phosphatidylcholine at different purity degrees (Phospholipon 90, 90% purity, soy lecithin (SL), 75% purity) and cholesterol (Chol), whereas niosomes w...
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abstract::Paclitaxel is not effective for treatment of brain cancers because it cannot cross the blood-brain barrier (BBB) due to efflux by P-glycoprotein (P-gp). In this work, glutathione-coated poly-(lactide-co-glycolide) (PLGA) nanoparticles (NPs) of paclitaxel were developed for brain targeting for treatment of brain cancer...
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abstract::Gene delivery systems face the problem not only of the route toward the cell and tissues in question, but also of the molecularly crowded environment of both the cytoplasm and the nucleus itself. One of the physical barriers in the cytoplasm for diffusing nanoparticles is an actin network. Here, we describe the findin...
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abstract::Toxoplasmic encephalitis (TE) is the most common clinical manifestation of reactivated infection with Toxoplasma gondii in immunocompromised patients that is lethal if untreated. The combination of pyrimethamine plus sulfadiazine or clindamycin is the standard therapy for the treatment of TE, but these combinations ar...
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abstract::The biodistribution of orally and intravenously administered archaeosomes in mice was compared to that of archaeosomes containing either coenzyme Q10 (archaeosome-CoQ10), polyethylene glycol (archaeosome-PEG), or PEG plus CoQ10 (archaeosome-PEG-CoQ10). The archaeosome formulations were prepared by a reverse-phase evap...
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abstract::The aim of this study was to evaluate the pharmacokinetics (PK), tissue distribution, and the specific drug targeting of cefpiramide sodium-loaded liposomes (CPMS-Lips) compared with cefpiramide sodium solution (CPMS-Sol) in mice. CPMS-Lips were prepared by reverse phase evaporation method. In the PK and biodistributi...
journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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更新日期:2021-01-22 00:00:00
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journal_title:Journal of drug targeting
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abstract::Rabies virus glycoprotein (RVG), a 505 amino acid type-1 glycoprotein, is responsible for the neurotrophic nature of the rabies virus infection. Despite varying reports in the literature as to which receptor is ultimately responsible for interaction of RVG with the nervous system, there is a strong argument for major ...
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abstract::Cytokine inhibiting drugs are much more effective when delivered intracellularly to phagocytic cells in the microencapsulated form. Dexamethasone is a powerful inhibitor of TNF-α cytokine through inhibition of NF-κB which is a gene regulator of multiple pro-inflammatory cytokines. We have determined the effect of micr...
journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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doi:10.1080/1061186X.2016.1200588
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journal_title:Journal of drug targeting
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doi:10.1080/10611860802295581
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abstract::Surface architecture of pharmaceutical nanocarriers (using polymeric micelles as an example) and the length of the spacer group through which specific ligand is attached to the carrier surface determine the interaction of ligand-bearing nanocarrier with cells. We have prepared surface-modified polyethyleneglycol-phosp...
journal_title:Journal of drug targeting
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doi:10.1080/10611860802230240
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journal_title:Journal of drug targeting
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doi:10.3109/10611869509015918
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abstract::Targeting of anti-tumor drugs to the urinary bladder for the treatment of bladder carcinoma may be useful, since these agents generally have a low degree of urinary excretion and are highly toxic elsewhere in the body. The anti-tumor drug doxorubicin was coupled to the low-molecular weight protein lysozyme via the aci...
journal_title:Journal of drug targeting
pub_type: 杂志文章
doi:10.1080/10611860290007568
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journal_title:Journal of drug targeting
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journal_title:Journal of drug targeting
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abstract::The aim of the present study was to develop a polymeric delivery system for water-insoluble drug oridonin. Amphiphilic block copolymers, poly(epsilon-caprolactone)-poly(ethylene glycol)-poly (epsilon-caprolactone) (PCL-PEO-PCL), were synthesized by ring-opening polymerization of caprolactone initiated by the hydroxyl ...
journal_title:Journal of drug targeting
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doi:10.1080/10611860802200938
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abstract::Highly lipophilic antitumor agent, palmitoyl rhizoxin (RS-1541), was incorporated into stable lipid emulsions about 100-1000nm in mean diameter consisting of triglyceride ODO and surfactant HCO-60. The pharmacokinetics of RS-1541 were studied after i.v. injection in mice, rats, rabbits, and dogs. Dog showed characteri...
journal_title:Journal of drug targeting
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