3.8 Article

Glutathione (GSH) Peptide Conjugated Magnetic Nanoparticles As Blood-Brain Barrier Shuttle for MRI-Monitored Brain Delivery of Paclitaxel

期刊

ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 5, 期 4, 页码 1677-1685

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.8b01420

关键词

shuttle peptides; magnetic nanoparticle; MRI monitored; brain delivery; biodegradability

资金

  1. Zanjan University of Medical Sciences [A-12-430-23]

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In drug delivery science, brain delivery is one of the most important challenges because of the low efficiency of the available treatments. Nowadays, shuttle peptides have attracted more attention because of lower price, reduced immunity, and increased chemical capability. Glutathione (GSH) is one of the blood brain barrier (BBB) shuttle peptides that has reached the most progressive steps in the path toward clinical application. This project discovered the possibility of GSH-conjugated IONPs as an MRI-monitored paclitaxel (PTX) delivery vehicle across the BBB using BALB/c mouse model. Synthesized shuttle peptide-conjugated nano particles were tracked over a certain time by MM. A one-pot method was used for preparation of IONPs@Asp to form functionalized nanoparticles with two functional groups for linkage of PTX, PEG, and then GSH on the surface of nanoparticles. Afterward, they were analyzed by XRD, TGA, FTIR, TEM, VSM, and DLS techniques. In addition, histological study were performed on the key organs. Here, we exhibit that (1) IONPs@Asp are stable and nontoxic to different cells; (2) conjugation of GSH to nanoparticles promotes their internalization to brain in vivo; (3) final formulation (IONPs@Asp-PTX-PEG-GSH) are effective in MM visualization; (4) IONPs@Asp-PTX-PEG-GSH begins to eliminate shortly afterward by the kidneys subsequently administration; (5) they were absorbed by liver, spleen, and especially by brain and simultaneously enhancing MM contrast. Thus, IONPs@Asp-PTX-PEG-GSH are promising MM-monitored paclitaxel (PTX) delivery vehicle across the BBB.

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