Macromolecular colloids of diblock poly(amino acids) that bind insulin

The diblock polymer poly(L-leucine-block-L-glutamate), bLE, was synthesized by acid hydrolysis of the ester poly(L-leucine-block-L-methyl glutamate). During the hydrolysis reaction the leucine block precipitates from the reac tion mixture, forming nanosized particulate structures. These particles can be purified and further suspended in water or in 0.15 M phosphate saline b uffer (PBS) to give stable, colloidal dispersions. TEM analysis shows the p redominant particle form to be that of platelets with a diameter of 200 nm. Smaller cylindrical or spherical particles form a relatively minor fractio n of the sample. After fractionation, analysis shows the platelets to be co mpositionally rich in leucine, while the spheres are glutamate-rich. H-1 NM R, CD, and X-ray diffraction indicate that the core of the platelets is com posed of crystalline, helical leucine segments. The poly(L-glutamate) polye lectrolyte brush extending out from the two faces of the disk stabilizes in dividual particles from flocculation. At pH 7.4, the nanoparticles (platele ts and cylinders) spontaneously adsorb proteins, such as insulin, directly from solution. Partial desorption of the protein in its native configuratio n can be induced by simple dilution. The reversibility of the insulin-nanop article complex is the basis for a potential new delivery system, (C) 1999 Academic Press.