MODIFICATION OF THE COPOLYMERS POLOXAMER-407 AND POLOXAMINE-908 CAN AFFECT THE PHYSICAL AND BIOLOGICAL PROPERTIES OF SURFACE-MODIFIED NANOSPHERES

Purpose, To investigate the effects of the modification of the copolym ers poloxamer 407 and poloxamine 908 on the physical and biological pr operties surface modified polystyrene nanospheres. Methods. A method t o modify poloxamer 407 and poloxamine 908, introducing a terminal amin e group to each PEO chain has been developed. The aminated copolymers can be subsequently radiolabelled with Iodinated (I-125) Bolton-Hunter reagent. The aminated copolymers were used to surface modify polystyr ene nanospheres. The physical and biological properties of the coated nanospheres were studied using particle size, zeta potential, in vitro non-parenchymal cell uptake and in vivo biodistribution experiments. Results. The presence of protonated amine groups in the modified copol ymers significantly affected the physical and biological properties of the resulting nanospheres, although the effects were copolymer specif ic. The protonated surface amine groups in both copolymers reduced the negative zeta potential of the nanospheres. Acetylation of the copoly mer's free amine groups resulted in the production of nanospheres with comparable physical properties to control unmodified copolymer coated nanospheres. In vivo, the protonated amine groups in the copolymers i ncreased the removal of the nanospheres by the liver and spleen, altho ugh these effects were more pronounced with the modified poloxamer 407 coated nanospheres. Acetylation of the amine groups improved the bloo d circulation time of the nanospheres providing modified poloxamine 90 8 coated nanospheres with comparable biological properties to control poloxamine 908 coated nanospheres. Similarly, modified poloxamer 407 c oated nanospheres had only slightly reduced circulation times in compa rison to control nanospheres. Conclusions, The experiments have demons trated the importance of copolymer structure on the biological propert ies of surface modified nanospheres. Modified copolymers, which posses s comparable properties to their unmodified forms, could be used in na nosphere systems where antibody fragments can be attached to the copol ymers, thereby producing nanospheres which target to specific body sit es.