Poly[N-(2-hydroxypropyl)methacrylamide] polymers diffuse in brain extracellular space with same tortuosity as small molecules

Integrative optical imaging was used to show that long-chain synthetic poly [N-(2-hydroxypropyl)methacrylamide] (PHPMA) polymers in a range of molecula r weights from 7.8 to 1057 kDa were able to diffuse through the extracellul ar space in rat neocortical slices. Tortuosity (square root of ratio of dif fusion coefficient in aqueous medium to that in brain) measured with such p olymers averaged 1.57, a value similar to that obtained previously with tet ramethylammonium, a small cation. When PHPMA was conjugated with bovine ser um albumin (BSA) to make a bulky polymer with molecular weight 176 kDa, the tortuosity rose to 2.27, a value similar to that obtained previously with BSA alone and with 70-kDa dextran. The method of image analysis was justifi ed with diffusion models involving spherical and nonspherical initial distr ibutions of the molecules.