Modulation of lymphatic distribution of subcutaneously injected poloxamer 407-coated nanospheres: the effect of the ethylene oxide chain configuration.
Lymphatic distribution of interstitially injected poloxamer 407-coated nanospheres (45 nm in diameter) is controlled by surface configuration of the ethylene oxide (EO) segments of the adsorbed copolymer. At low poloxamer surface coverage, EO tails spread laterally on a nanosphere surface and assume a 'flat or mushroom-like' configuration. Such entities drain rapidly from the subcutaneous site of injection into the initial lymphatic, when compared to uncoated nanospheres, and subsequently are captured by scavengers of the regional lymph nodes. In vitro experiments have also confirmed that such entities are prone to phagocytosis. When the equilibrium poloxamer concentration is at 75 microg/ml or greater the EO chains become more closely packed and project outward from the nanosphere surface. These surface-engineered nanospheres drain faster than those with EO chains in mushroom configurations into the initial lymphatic, escape clearance by lymph node macrophages, reach the systemic circulation, and remain in the blood for prolonged periods. These experiments provide a rational approach for the design and engineering of nano-vehicles for optimal lymphatic targeting and are discussed.
Moghimi
S M
SM
Molecular Targeting and Polymer Toxicology Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK. s.m.moghimi@brighton.ac.uk
D000818:Animals; D005027:Ethylene Oxide / Q000737:chemistry*; D008208:Lymphatic System / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D036103:Nanotechnology; D020442:Poloxamer / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D020442:Poloxamer; D005027:Ethylene Oxide