ACCUMULATION OF PROTEIN-LOADED LONG-CIRCULATING MICELLES AND LIPOSOMES IN SUBCUTANEOUS LEWIS LUNG-CARCINOMA IN MICE

Purpose. The purpose of our work was to compare the biodistribution an d 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) an d incorporated into both polyethyleneglycol (MW 5000)-distearoyl phosp hatidyl ethanolamine (PEG-DSPE) micelles (< 20 nm) and PEG-DSPE-modifi ed long-circulating liposomes (ca. 100 nm). The protein was labeled wi th In-111 via protein-attached diethylene triamine pentaacetic acid (D TPA), and samples of STI-containing liposomes or micelles were injecte d via the tail vein into mice bearing subcutaneously-established Lewis lung carcinoma. At appropriate time points, mice were sacrified and t he radioactivity accumulated in the tumor and main organs was determin ed. Results. STI incorporated into PEG-lipid micelles accumulates in s ubcutaneously 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 mice lles, are more efficient in the delivery of protein to Lewis lune carc inoma than larger long-circulating liposomes.