期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 62, 期 -, 页码 523-530出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2013.10.004
关键词
Methotrexate; Nanogel; Brain drug delivery; Surface modification; Release kinetic; Blood-brain barrier
资金
- Tehran University of Medical Sciences (TUMS) [11852]
- Zanjan University of Medical Sciences
Methotrexate-loaded hydrogel nanoparticles were prepared and after in vitro characterization, their transport across blood-brain barrier was investigated in vivo in intact animals in this study. The ionic gelation method was used for preparation of drug-loaded nanogels, after optimized by a systematic multi-objective optimization approach. After surface-modification with polysorbate 80, nanoparticles with the final particle size, poly-dispersity index (PDI), loading efficiency (LE) and loading capacity (LC) of 118.54 +/- 15.93 nm, 0.35 +/- 0.05, 61.82 +/- 6.84%, and 53.68 +/- 3.09% were obtained, respectively. The in vitro drug release study indicated non-Fickian diffusion kinetic, apparently governed by both diffusion of the drug out of the nanoparticles and swelling/disintegration of the polymeric network as characterized by a Weibull model for both surface-treated and untreated nanogels. After intravenous administration of surface-modified and unmodified nanogels compared to the free drug, all with the same dose of 25 mg/kg, remarkably higher brain concentrations of methotrexate were achieved with the nanogel formulations in comparison to the free drug (in some cases, more than 10-fold); but there were no significant differences between the surface-modified and unmodified nanogels in all the time points tested. (C) 2013 Elsevier B.V. All rights reserved.
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