Abstract:
:Chitosan-based hydrogel nanoparticles provide a higher brain concentration of methotrexate (MTX) following IV administration in comparison with the drug's simple solution. The present study investigates the mechanism of this phenomenon, focusing on the possible role of P-gp. A previously developed MTX containing chitosan nanogel was fabricated and characterised. Then 48 rats were divided into four groups: two receiving nanogels and two receiving solution of MTX, while 1 of each two had received a verapamil dose 30 min before MTX. Then, rats were sacrificed in four time points in triplicate, and MTX concentration in their plasma and brains were quantified and were compared statistically. Following IV injection, spherical nanogels with a mean diameter of <200 nm, zeta potential of 22.8 ± 6.55 mv, Loading efficiency of 72.03 ± 0.85, and loading capacity of 1.41 ± 0.02 produce a significantly higher brain concentration compared with the simple solution. Furthermore, those receiving verapamil presented a higher brain concentration. It seems that in the short term after drug administration (<1 h) nanogels facilitate MTX passage by providing a higher concentration of drug in contact with BBB, but in a more extended period nanogels pass the BBB and release their content beyond that.
journal_name
Int J Biol Macromoljournal_title
International journal of biological macromoleculesauthors
Pourtalebi Jahromi L,Moghaddam Panah F,Azadi A,Ashrafi Hdoi
10.1016/j.ijbiomac.2018.12.093subject
Has Abstractpub_date
2019-03-15 00:00:00pages
785-790eissn
0141-8130issn
1879-0003pii
S0141-8130(18)35649-6journal_volume
125pub_type
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