Poly[N-(2-hydroxypropyl)methacrylamide] polymers diffuse in brain extracellular space with same tortuosity as small molecules
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.
Grant support
NS 28642
NINDS NIH HHS - United States
PubMed
11159424
PubMed Central
PMC1301255
DOI
10.1016/s0006-3495(01)76036-5
PII: S0006-3495(01)76036-5
Knihovny.cz E-resources
- MeSH
- Dextrans chemistry pharmacokinetics MeSH
- Diffusion MeSH
- Extracellular Space metabolism MeSH
- Microscopy, Fluorescence MeSH
- Rats MeSH
- Polymethacrylic Acids chemistry pharmacokinetics MeSH
- Models, Neurological MeSH
- Molecular Weight MeSH
- Neocortex metabolism MeSH
- Optics and Photonics MeSH
- Rats, Sprague-Dawley MeSH
- Serum Albumin, Bovine chemistry pharmacokinetics MeSH
- Cattle MeSH
- Drug Delivery Systems MeSH
- In Vitro Techniques MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Cattle MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- Names of Substances
- Dextrans MeSH
- Duxon MeSH Browser
- Polymethacrylic Acids MeSH
- Serum Albumin, Bovine MeSH
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.
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Diffusion in brain extracellular space
