title: Size dependent biodistribution and SPECT imaging of (111)In-labeled polymersomes.
abstract: Polymersomes, self-assembled from the block copolymer polybutadiene-block-poly(ethylene glycol), were prepared with well-defined diameters between 90 and 250 nm. The presence of ~1% of diethylene triamine penta acetic acid on the polymersome periphery allowed to chelate radioactive (111)In onto the surface and determine the biodistribution in mice as a function of both the polymersome size and poly(ethylene glycol) corona thickness (i.e., PEG molecular weight). Doubling the PEG molecular weight from 1 kg/mol to 2 kg/mol did not change the blood circulation half-life significantly. However, the size of the different polymersome samples did have a drastic effect on the blood circulation times. It was found that polymersomes of 120 nm and larger become mostly cleared from the blood within 4 h, presumably due to recognition by the reticuloendothelial system. In contrast, smaller polymersomes of around 90 nm circulated much longer. After 24 h more than 30% of the injected dose was still present in the blood pool. This sharp transition in blood circulation kinetics due to size is much more abrupt than observed for liposomes and was additionally visualized by SPECT/CT imaging. These findings should be considered in the formulation and design of polymersomes for biomedical applications. Size, much more than for liposomes, will influence the pharmacokinetics, and therefore, long circulating preparations should be well below 100 nm.
authors.affiliation: Institute for Molecules and Materials, Radboud University Nijmegen , Heijendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands.
authors.forename: René P
authors.initials: RP
authors.lastname: Brinkhuis
authors.forename: Katica
authors.initials: K
authors.lastname: Stojanov
authors.forename: Peter
authors.initials: P
authors.lastname: Laverman
authors.forename: Jos
authors.initials: J
authors.lastname: Eilander
authors.forename: Inge S
authors.initials: IS
authors.lastname: Zuhorn
authors.forename: Floris P J T
authors.initials: FP
authors.lastname: Rutjes
authors.forename: Jan C M
authors.initials: JC
authors.lastname: van Hest
mesh_terms: D000818:Animals; D002070:Butadienes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D020724:Elastomers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007205:Indium Radioisotopes / Q000032:analysis; D008081:Liposomes / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002070:Butadienes; D020724:Elastomers; D007205:Indium Radioisotopes; D008081:Liposomes; D011092:Polyethylene Glycols; C028834:polybutadiene