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      Targeted delivery of doxorubicin using stealth liposomes modified with transferrin.

      International Journal of Pharmaceutics

      chemistry, Xenograft Model Antitumor Assays, Area Under Curve, Cell Line, Tumor, Cell Survival, drug effects, Doxorubicin, administration & dosage, Animals, metabolism, pharmacology, therapeutic use, Drug Delivery Systems, methods, Flow Cytometry, Humans, Inhibitory Concentration 50, Liposomes, Male, Mice, Mice, Inbred ICR, Microscopy, Confocal, Neoplasms, drug therapy, pathology, Particle Size, Rats, Rats, Inbred Strains, Tissue Distribution, Transferrin, Animal Structures

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          Abstract

          Site-specific delivery of drugs and therapeutics can significantly reduce drug toxicity and increase the therapeutic effect. Transferrin (Tf) is one suitable ligand to be conjugated to drug delivery systems to achieve site-specific targeting, due to its specific binding to transferrin receptors (TfR), highly expressed on the surfaces of tumor cells. Stealth liposomes are effective vehicles for drugs, genes and vaccines and can be easily modified with proteins, antibodies, and other appropriate ligands, resulting in attractive formulations for targeted drug delivery. In this study, we prepared doxorubicin-loaded stealth liposomes (Tf-SL-DOX) by film dispersion followed by ammonium sulphate gradient method, then conjugated Tf to the liposome surface by an amide bound between DSPE-PEG(2000)-COOH and Tf. The results of the intracellular uptake study indicated that Tf-modified SL was able to enhance the intracellular uptake of the entrapped DOX by HepG2 cells compared to SL-DOX. We studied tissue distribution and therapeutic effects of Free DOX, SL-DOX and Tf-SL-DOX in tumor-bearing mice and pharmacokinetics in rats. The pharmacokinetic behavior of Tf-SL-DOX in the plasma was closed to SL-DOX. Administration of Tf-SL-DOX to tumor-bearing mice could be used to deliver DOX effectively to the targeted site, significantly increasing DOX concentration in tumor and decreasing DOX concentration in heart and kidney. In summary, our study indicated that the Tf-coupled PEG liposomes (Tf-SL) could be as the targeted carriers to facilitate the delivery of the encapsulated anticancer drugs into tumor cells by receptor-mediated way.

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          Journal
          19429296
          10.1016/j.ijpharm.2009.01.023

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