We evaluated the BBB permeability of FITC-dextran in the Transwell system. Its permeation was severely obstructed due to the highly hydrophilic properties of dextrans (logP = -2.0 for FITC-dextran 4 kDa), their extensive branching (MW > 10 kDa), and huge hydrodynamic radius (RH ≈ 85 Å). Did anyone analyze the effect of RH at the BBB?
Watson (Watson et al. BMC Neuroscience 2013, 14:59) looked at permeability of dextrans ranging from 4 kDa-70 kDa in a transwell system. McGowan volumes and BBB penetration have also been investigated (Gratton, J Pharm Pharmacol 1997, 49(12): 1211), though this was used in conjunction with other molecular descriptors.
Charles Nicholson and more lately Robert Thorne have investigated molecular radius effects on solute diffusion within brain tissue, not sure if they looked at BBB permeation though.
Alex Avdeef has collected a large data base of molecular descriptors and BBB permeability as well so he may be worth contacting to ask if he has any information. He is on Research gate so you should find him easily enough.
There is a study from the laboratory of Bingmei Fu (PMID: 20434157) which contains graphs on dextran permeability (4-70 kDa) and Stokes radius. They use both own meausred data (but the parameters of their model is not included in the pdf version of the paper) and literature data.
In addition to size, the charge of dextran is also important, there are 2 culture studies indicating that anionic charge of dextran even further blocks brain endothelial layer penetration (PMID: 1695819, PMID: 2434625).
Regards, Maria
How you can justify the better permeation properties for SWCNT or MWCNT (Shityakov et al., unpublished) with bigger RH value? Using the SWCNT length (L) and radius (R) values (aspect ratio 100 and R = 0.45 nm for arbitrary SWCNT), the calculated hydrodynamic radius (L/(ln(L/R)+0.32) is found to be 17.47 nm (175 Å vs. 85 Å) depending on the chosen value of nanotube radius.
Dear Sergey,
I am not familiar with your experiments and your SWCNTs. What I wrote on dextrans and the BBB, is valid for all NPs and most probably for SWCNTs. RH is not the only parameter determining the crossing of particles across barriers. In addition to size, charge, shape, chemical and surface properties are equally important.
One aspect you need to consider, that routes across barriers can be not only paracellular, determined by tight junctions, but transcellular, too.
I suggest you to check, if SWCNTs are able to induce transcellular transport. This pathway is size-independent. I attach a book chapter of mine where you can find some examples of different BBB transport pathways.
regards,
M.
suggested BBB reviews:
1: Abbott NJ. Blood-brain barrier structure and function and the challenges for
CNS drug delivery. J Inherit Metab Dis. 2013 May;36(3):437-49. PubMed PMID: 23609350.
2: Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and
function of the blood-brain barrier. Neurobiol Dis. 2010 Jan;37(1):13-25. PubMed PMID: 19664713.
3: Abbott NJ, Rönnbäck L, Hansson E. Astrocyte-endothelial interactions at the
blood-brain barrier. Nat Rev Neurosci. 2006 Jan;7(1):41-53. Review. PubMed PMID:
16371949.
Thank you. Yes, indeed, the SWCNT structure has the ability to permeate the BBB via transcellular route due to its high lipophilic properties. We did some experiments to compare MWCNT-FITC and FITC-dextran 150 in this regard, but these two nanoparticles are not quite comparable in terms of RH though.
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