@article {24, title = {Immunomicelles: targeted pharmaceutical carriers for poorly soluble drugs.}, journal = {Proc Natl Acad Sci U S A}, volume = {100}, year = {2003}, month = {2003 May 13}, pages = {6039-44}, abstract = {

To prepare immunomicelles, new targeted carriers for poorly soluble pharmaceuticals, a procedure has been developed to chemically attach mAbs to reactive groups incorporated into the corona of polymeric micelles made of polyethylene glycol-phosphatidylethanolamine conjugates. Micelle-attached antibodies retained their ability to specifically interact with their antigens. Immunomicelles with attached antitumor mAb 2C5 effectively recognized and bound various cancer cells in vitro and showed an increased accumulation in experimental tumors in mice when compared with nontargeted micelles. Intravenous administration of tumor-specific 2C5 immunomicelles loaded with a sparingly soluble anticancer agent, taxol, into experimental mice bearing Lewis lung carcinoma resulted in an increased accumulation of taxol in the tumor compared with free taxol or taxol in nontargeted micelles and in enhanced tumor growth inhibition. This family of pharmaceutical carriers can be used for the solubilization and enhanced delivery of poorly soluble drugs to various pathological sites in the body.

}, keywords = {Animals, Antibodies, Biological Transport, Breast Neoplasms, Drug Carriers, Drug Design, Female, Fluoresceins, Freeze Fracturing, Humans, Indium Radioisotopes, Kinetics, Lung Neoplasms, Lymphoma, Metabolic Clearance Rate, Mice, Micelles, Microscopy, Electron, Phosphatidylethanolamines, Polyethylene Glycols, Solubility, Tumor Cells, Cultured}, issn = {0027-8424}, doi = {10.1073/pnas.0931428100}, author = {Torchilin, Vladimir P and Lukyanov, Anatoly N and Gao, Zhonggao and Papahadjopoulos-Sternberg, Brigitte} } @article {22, title = {Micelles from polyethylene glycol/phosphatidylethanolamine conjugates for tumor drug delivery.}, journal = {J Control Release}, volume = {91}, year = {2003}, month = {2003 Aug 28}, pages = {97-102}, abstract = {

Micelles prepared from polyethylene glycols of various lengths conjugated with phosphatidylethanolamine (PEG-PE) were loaded with various poorly soluble anticancer agents. PEG-PE micelles selectively accumulated in Lewis lung carcinoma (LLC) tumors implanted in mice. Modification of the micelles with tumor specific antibodies further enhanced the efficiency of tumor accumulation.

}, keywords = {Animals, Antineoplastic Agents, Drug Delivery Systems, Enzyme-Linked Immunosorbent Assay, Excipients, Female, Mice, Mice, Inbred C57BL, Micelles, Neoplasms, Particle Size, Phosphatidylethanolamines, Polyethylene Glycols, Solubility}, issn = {0168-3659}, author = {Lukyanov, Anatoly N and Gao, Zhonggao and Torchilin, Vladimir P} } @article {26, title = {Polyethylene glycol-diacyllipid micelles demonstrate increased acculumation in subcutaneous tumors in mice.}, journal = {Pharm Res}, volume = {19}, year = {2002}, month = {2002 Oct}, pages = {1424-9}, abstract = {

PURPOSE: The purpose of this work is to study the potential of micelles prepared from amphiphilic polyethelene glycol/phosphatidylethanolamine (PEG-PE) conjugates as a particulate drug delivery system capable of accumulation in tumors via the enhanced permeability and retention (EPR) effect.

METHODS: Micelles were prepared from PEGs of different molecular lengths conjugated with PE. The micelles were characterized by fluorescence-based critical micellization concentration (CMC) measure ments, dynamic light scattering, and HPLC. Blood clearance an tumor accumulation of 111In-labeled micelles were studied in mic with subcutaneously established Lewis lung carcinoma (LLC) and EL4 T lymphoma (EL4) tumors.

RESULTS: Various versions of PEG-PE conjugates with PEG blocks ranging from 750 to 5000 Da formed very stable low CMC micelles at all concentrations down to 10(-5) M. The size of the micelles varie between 7 and 35 nm depending on the length of the PEG block. Micelles remained intact after prolonged incubation with the blood serum. Upon intravenous administration into mice, the micelles demonstrated circulation longevity, and they efficiently and selectively accumulated in both subcutaneous Lewis lung carcinoma and EL4 T lymphoma tumors.

CONCLUSIONS: PEG-PE conjugates form very stable, long-circulating micelles. These micelles efficiently accumulate in tumors in vivo an may potentially be used as a tumor-specific delivery system for poorly soluble anticancer drugs.

}, keywords = {Animals, Carcinoma, Lewis Lung, Female, Injections, Subcutaneous, Mice, Mice, Inbred C57BL, Micelles, Phosphatidylethanolamines, Polyethylene Glycols, Tumor Cells, Cultured, Xenograft Model Antitumor Assays}, issn = {0724-8741}, author = {Lukyanov, Anatoly N and Gao, Zhonggao and Mazzola, Laureen and Torchilin, Vladimir P} }