The polyoxyethylene/polyoxypropylene block co‐polymer Poloxamer‐407 selectively redirects intravenously injected microspheres to sinusoidal endothelial cells of rabbit bone marrow

Small colloidal particulates (150 nm and below, in diameter) can be redirected specifically to the rabbit bone marrow following intravenous administration by coating their surface with the block co‐polymer poloxamer‐407, a non‐ionic surfactant. The coated colloids are sequestered by the sinusoidal endothelial cells of the bone marrow and are accumulated in dense bodies within these cells. The uptake of poloxamer‐4O7‐coated colloids by marrow eondothelial cells suggests that the steric repulsive barrier, imposed by the polyoxyethylene segment of the polymer, to particle‐cell interaction can apparently be overcome by a specific interaction mechanism(s) with the cell surface. Such a dramatic uptake cannot be achieved with other block co‐polymers of similar structure to poloxamer‐407. The application of the current model for the site‐specific targeting or drug carriers to bone marrow and the prevention of the adherence of metastases of tumours which selectively colonize the bone marrow endothelium is discussed.

[1]  S. Moghimi,et al.  Differential properties of organ-specific serum opsonins for liver and spleen macrophages. , 1989, Biochimica et biophysica acta.

[2]  S. Michelson,et al.  The migration of blood cells of the bone marrow through the sinusoidal wall , 1971, Journal of morphology.

[3]  D. Rawlins,et al.  Adsorption characteristics of certain polyoxyethylene-polyoxypropylene block co-polymers on polystyrene latex , 1979 .

[4]  V. Torchilin,et al.  Characterization of in vivo immunoliposome targeting to pulmonary endothelium. , 1990, Journal of pharmaceutical sciences.

[5]  M. Kataoka,et al.  Identification of lectin-like substances recognizing galactosyl residues of glycoconjugates on the plasma membrane of marrow sinus endothelium. , 1985, Blood.

[6]  R. Starzyk,et al.  Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[7]  R. Müller,et al.  The organ distribution and circulation time of intravenously injected colloidal carriers sterically stabilized with a block copolymer--poloxamine 908. , 1987, Life sciences.

[8]  K. Caldwell,et al.  Sedimentation field flow fractionation in the determination of surface concentration of adsorbed materials , 1991 .

[9]  G. Nicolson Cancer metastasis: tumor cell and host organ properties important in metastasis to specific secondary sites. , 1988, Biochimica et biophysica acta.

[10]  J. Bitran Bone marrow, structure and function , 1983 .

[11]  S. Davis,et al.  Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating. , 1991, Biochemical and biophysical research communications.

[12]  S. Davis Microspheres and drug therapy : pharmaceutical, immunological, and medical aspects , 1984 .

[13]  C. Gamba-Vitalo,et al.  Bone Marrow: Structure and Function , 1984, The Yale Journal of Biology and Medicine.

[14]  R. P. Becker,et al.  Endocytosis by endothelial phagocytes: uptake of bovine serum albumin-gold conjugates in bone marrow. , 1984, Journal of ultrastructure research.

[15]  J. M. Yoffey,et al.  Ultrastructure of reticuloendothelial elements in guinea-pig bone marrow. , 1968, Journal of anatomy.

[16]  S. Davis,et al.  Targeting of colloidal particles to the bone marrow. , 1987, Life sciences.

[17]  S. Davis,et al.  The organ uptake of intravenously administered colloidal particles can be altered using a non‐ionic surfactant (Poloxamer 338) , 1984, FEBS letters.

[18]  R. Mahley,et al.  Chylomicron metabolism. Chylomicron uptake by bone marrow in different animal species. , 1989, The Journal of biological chemistry.

[19]  Teh‐Siu Huang,et al.  PASSAGE OF FOREIGN PARTICLES THROUGH THE SINUSOIDAL WALL OF THE RABBIT BONE MARROW—AN ELECTRON MICROSCOPIC STUDY , 1971, Acta pathologica japonica.

[20]  R. P. Becker,et al.  Endocytosis, transfer tubules, and lysosomal activity in myeloid sinusoidal endothelium. , 1975, Journal of ultrastructure research.