Unlabelled: Understanding hepatitis C virus (HCV) replication has been limited by access to serial samples of liver, the primary site of viral replication. Our understanding of how HCV replicates and develops drug-resistant variants in the liver is limited. We studied 15 patients chronically infected with genotype 1 HCV treated with telaprevir (TVR)/pegylated-interferon alpha/ribavirin.
View Article and Find Full Text PDFLong-circulating liposomes loaded with doxorubicin (Dox) were additionally modified with the prostate cell-specific monoclonal antibody 5D4 (mAb 5D4). The resultant Dox-loaded 5D4-immunoliposomes specifically recognized prostate cancer cell lines of several different types expressing the mAb 5D4 antigen, PSMA, and significantly enhanced cytotoxicity toward these cells compared with the non-targeted Dox-liposomes in vitro while no increased toxicity was observed toward non-prostate (lung) cancer cell line.
View Article and Find Full Text PDFSurface 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-phosphatidylethanolamine (PEG-PE) micelles containing TATp attached to PEG-PE with a PEG block longer or shorter (TATp-PEG(1000)-PE or TATp-PEG(3400)-PE) than the PEG block in the main micelle-forming material (PEG(750)-PE and/or PEG(2000)-PE). The length of the PEG spacer in TATp-PEG-PE should allow for a non-hindered interaction of TATp with the cell surface, but it should not be too long to allow for the conformational "folding in" of TATp moiety inside the PEG globule making it unable to interact with the cells.
View Article and Find Full Text PDFTwo poorly soluble, potent anti-cancer drugs, paclitaxel and camptothecin, were successfully solubilized by mixed micelles of polyethylene glycol-phosphatidyl ethanolamine (PEG-PE) and vitamin E. Drug-containing micelles were additionally modified with anti-nucleosome monoclonal antibody 2C5 (mAb 2C5), which can specifically bring micelles to tumor cells in vitro. The optimized micelles had an average size of about 13-22 nm and the immuno-modification of micelles did not significantly change it.
View Article and Find Full Text PDFStable nanocolloids of insoluble drugs with very high drug content (up to 90% wt) can be easily and reproducibly prepared through the application of the layer-by-layer (LbL) technology, alternate adsorption of oppositely charged polyelectrolytes on the surface of drug nanoparticles produced by ultrasonication of larger drug crystals. Such polymeric coating prevents drug nanoparticle aggregation and creates a firm polymeric shell on their surface. Drug release rate from such nanocolloidal particles can be easily controlled by assembling multilayer shells with variable shell density and thickness.
View Article and Find Full Text PDFMixed micelles prepared of poly(ethylene glycol)2000-phosphatidyl ethanolamine conjugate (PEG(2000)-PE) and d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) in 1:1 molar ratio have been investigated. Micelle formation was confirmed by NMR spectroscopy. CMC of the micelles was found to be 1.
View Article and Find Full Text PDFLiposome loading with Gd via the membrane-incorporated polychelating amphiphilic polymers (PAPs) significantly increases the Gd content and relaxivity (T1 parameter) of PEGylated liposomes, which can be used as contrast agents for magnetic resonance imaging (MRI). Here, we demonstrate that such Gd-containing liposomes can be additionally modified with the monoclonal anticancer antibody 2C5 (mAb 2C5) possessing the nucleosome(NS)-restricted specificity via the PEG spacer. Liposome-bound antibody preserves its specific activity (ELISA) and such Gd-loaded PEGylated 2C5-immunoliposomes specifically recognize various cancer cells in vitro and target an increased amount of Gd to their surface compared to antibody-free Gd-liposomes or Gd-liposomes modified with tumor nonspecific antibody.
View Article and Find Full Text PDFDextran-polyethylene glycol (PEG) conjugates were synthesized by activating dextran hydroxy groups with carbonyldiimidazole, introducing amino groups by attaching ethylenediamine, and reacting amino groups with a succinimidyl-activated derivative of PEG. Conjugates with an average of 12 and 21 PEG (5 kDa) residues per single dextran (73 kDa) molecule were prepared. These conjugates have circulation half-lives of 5.
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