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 molecular weights from 7.8 to 1057 kDa were able to diffuse through the extracellular space in rat neocortical slices. Tortuosity (square root of ratio of diffusion coefficient in aqueous medium to that in brain) measured with such polymers averaged 1.57, a value similar to that obtained previously with tetramethylammonium, a small cation. When PHPMA was conjugated with bovine serum 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 justified with diffusion models involving spherical and nonspherical initial distributions of the molecules.
Prokopová-Kubinová
S
S
Department of Neuroscience, Second Faculty of Medicine, Charles University, and Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic.
Vargová
L
L
Tao
L
L
Ulbrich
K
K
Subr
V
V
Syková
E
E
Nicholson
C
C
D000818:Animals; D002417:Cattle; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics; D004058:Diffusion; D016503:Drug Delivery Systems; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence; D008959:Models, Neurological; D008970:Molecular Weight; D019579:Neocortex / Q000378:metabolism*; D055095:Optics and Photonics; D011109:Polymethacrylic Acids / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000493:pharmacokinetics
D003911:Dextrans; D011109:Polymethacrylic Acids; D012710:Serum Albumin, Bovine; C011533:Duxon