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Accumulation of Protein-Loaded Long-Circulating Micelles and Liposomes in Subcutaneous Lewis Lung Carcinoma in Mice

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Abstract

Purpose. The purpose of our work was to compare the biodistribution and tumor accumulation of a liposome- or micelle-incorporated protein in mice bearing subcutaneously-established Lewis lung carcinoma.

Methods. A model protein, soybean trypsin inhibitor (STI) was modified with a hydrophobic residue of N-glutaryl-phosphatidyl-ethanolamine (NGPE) and incorporated into both polyethyleneglycol(MW 5000)-distearoyl phosphatidyl ethanolamine (PEG-DSPE) micelles (< 20 nm) and PEG-DSPE-modified long-circulating liposomes (ca. 100 nm). The protein was labeled with 111In via protein-attached diethylene triamine pentaacetic acid (DTPA), and samples of STI-containing liposomes or micelles were injected via the tail vein into mice bearing subcutaneously-established Lewis lung carcinoma. At appropriate time points, mice were sacrified and the radioactivity accumulated in the tumor and main organs was determined.

Results. STI incorporated into PEG-lipid micelles accumulates in sub-cutaneously established Lewis lung carcinoma in mice better than the same protein anchored in long-circulating PEG-liposomes.

Conclusions. Small-sized long-circulating delivery systems, such as PEG-lipid micelles, are more efficient in the delivery of protein to Lewis lung carcinoma than larger long-circulating liposomes.

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Authors and Affiliations

  1. Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Center for Imaging and Pharmaceutical Research, Charlestown, Massachusetts, 02129

    Volkmar Weissig, Kathleen R. Whiteman & Vladimir P. Torchilin

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  1. Volkmar Weissig
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  2. Kathleen R. Whiteman
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  3. Vladimir P. Torchilin
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Correspondence to Vladimir P. Torchilin.

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Weissig, V., Whiteman, K.R. & Torchilin, V.P. Accumulation of Protein-Loaded Long-Circulating Micelles and Liposomes in Subcutaneous Lewis Lung Carcinoma in Mice. Pharm Res 15, 1552–1556 (1998). https://doi.org/10.1023/A:1011951016118

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