Selective delivery of adriamycin to a solid tumor using a polymeric micelle carrier system.

The anticancer drug, adriamycin (ADR), was incorporated by physical entrapment into polymeric micelles for selective delivery to a murine solid tumor colon adenocarcinoma 26 (C 26). In vivo antitumor activity of ADR was greatly enhanced by this incorporation into polymeric micelles. Using one polymeric micelle delivery system, the tumor completely disappeared at two doses, while free ADR exhibited a fair inhibition effect on tumor growth only at the maximum tolerated dose. Biodistribution analysis revealed that the physically entrapped micellar ADR accumulated at tumor sites in a highly selective manner. These results indicate that these polymeric micelles are a promising system for delivering hydrophobic anticancer drugs selectively to solid tumor sites using a passive targeting mechanism.

[1]  T. Okano,et al.  Characterization of physical entrapment and chemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery to a solid tumor. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[2]  Teruo Okano,et al.  Block copolymer micelles for drug delivery: Loading and release of doxorubicin , 1997 .

[3]  T. Okano,et al.  Targetable drug carriers: present status and a future perspective , 1996 .

[4]  I. Pastan,et al.  Treatment of advanced solid tumors with immunotoxin LMB–1: An antibody linked to Pseudomonas exotoxin , 1996, Nature Medicine.

[5]  H. Dvorak,et al.  Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. , 1995, The American journal of pathology.

[6]  T. Okano,et al.  Improved synthesis of adriamycin-conjugated poly (ethylene oxide)-poly (aspartic acid) block copolymer and formation of unimodal micellar structure with controlled amount of physically entrapped adriamycin , 1994 .

[7]  T. Okano,et al.  Block copolymer micelles as vehicles for hydrophobic drugs , 1994 .

[8]  N. Van Rooijen,et al.  Effect of liposome size on the circulation time and intraorgan distribution of amphipathic poly(ethylene glycol)-containing liposomes. , 1994, Biochimica et biophysica acta.

[9]  Teruo Okano,et al.  Enhanced tumor accumulation and prolonged circulation times of micelle-forming poly(ethylene oxide-aspartate) block copolymer-Adriamycin conjugates , 1994 .

[10]  P. Trail,et al.  Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates. , 1993, Science.

[11]  F. Martin,et al.  Pharmacokinetics and therapeutics of sterically stabilized liposomes in mice bearing C-26 colon carcinoma. , 1992, Cancer research.

[12]  H. Dvorak,et al.  Pathways of macromolecular tracer transport across venules and small veins. Structural basis for the hyperpermeability of tumor blood vessels. , 1992, Laboratory investigation; a journal of technical methods and pathology.

[13]  Alexander V. Kabanov,et al.  A new class of drug carriers: micelles of poly(oxyethylene)-poly(oxypropylene) block copolymers as microcontainers for drug targeting from blood in brain☆ , 1992 .

[14]  H. Maeda,et al.  Conjugates of anticancer agents and polymers: advantages of macromolecular therapeutics in vivo. , 1992, Bioconjugate chemistry.

[15]  M. Woodle,et al.  Sterically stabilized liposomes. , 1992, Biochimica et biophysica acta.

[16]  D. Coulter,et al.  Selective in vivo localization of daunorubicin small unilamellar vesicles in solid tumors. , 1992, Cancer research.

[17]  A. Rolland,et al.  New macromolecular carriers for drugs. I. Preparation and characterization of poly(oxyethylene‐b‐isoprene‐b‐oxyethylene) block copolymer aggregates , 1992 .

[18]  A. Gabizon,et al.  Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times. , 1991, Biochimica et biophysica acta.

[19]  T. Okano,et al.  Toxicity and antitumor activity against solid tumors of micelle-forming polymeric anticancer drug and its extremely long circulation in blood. , 1991, Cancer research.

[20]  A. Gabizon,et al.  Effect of liposome composition and other factors on the targeting of liposomes to experimental tumors: biodistribution and imaging studies. , 1990, Cancer research.

[21]  T. Okano,et al.  Characterization and anticancer activity of the micelle-forming polymeric anticancer drug adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer. , 1990, Cancer research.

[22]  D. Knook,et al.  Sinusoidal endothelial cells of the liver: fine structure and function in relation to age. , 1990, Journal of electron microscopy technique.

[23]  J. Murray,et al.  Lack of comparability between binding of monoclonal antibodies to melanoma cells in vitro and localization in vivo. , 1989, Journal of the National Cancer Institute.

[24]  W. Laird,et al.  Chemical modification of recombinant interleukin 2 by polyethylene glycol increases its potency in the murine Meth A sarcoma model. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[25]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[26]  J. Cummings,et al.  Disposition kinetics of adriamycin, adriamycinol and their 7-deoxyaglycones in AKR mice bearing a sub-cutaneously growing ridgway osteogenic sarcoma (ROS). , 1986, European journal of cancer & clinical oncology.

[27]  H. Dvorak,et al.  Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. , 1983, Science.

[28]  J. Kopeček,et al.  Polymers containing enzymatically degradable bonds, 1. Chymotrypsin catalyzed hydrolysis of p‐nitroanilides of phenylalanine and tyrosine attached to side‐chains of copolymers of N‐(2‐hydroxypropyl)methacrylamide , 1981 .

[29]  F. Davis,et al.  Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. , 1977, The Journal of biological chemistry.

[30]  E. P. Denine,et al.  Comparative pharmacokinetics of daunomycin and adriamycin in several animal species. , 1972, Cancer research.

[31]  J. Furth,et al.  Direct Determinations of Plasma, Cell, and Organ-Blood Volumes in Normal and Hypervolemic Mice , 1950, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[32]  K. Ulbrich,et al.  Influence of molecular weight on passive tumour accumulation of a soluble macromolecular drug carrier. , 1995, European journal of cancer.

[33]  David Putnam,et al.  Polymer conjugates with anticancer activity , 1995 .

[34]  Kazuya Okamoto,et al.  composition-dependent in vivo antitumor activity of adriamycin-conjugated polymeric micelle against murine colon adenocarcinoma 26 , 1993 .