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-407-coated colloids by marrow endothelial 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 of drug carriers to bone marrow and the prevention of the adherence of metastases of tumours which selectively colonize the bone marrow endothelium is discussed.
Porter
C J
CJ
Department of Pharmaceutical Sciences, University of Nottingham, UK.
Moghimi
S M
SM
Illum
L
L
Davis
S S
SS
D000818:Animals; D001853:Bone Marrow / Q000648:ultrastructure; D001854:Bone Marrow Cells; D004337:Drug Carriers; D004727:Endothelium / Q000166:cytology / Q000648:ultrastructure; D007275:Injections, Intravenous; D008854:Microscopy, Electron; D008863:Microspheres; D011060:Poloxalene / Q000494:pharmacology*; D011817:Rabbits
D004337:Drug Carriers; D011060:Poloxalene