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

Abstract

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 nanoparticles were tracked over a certain time by MRI. 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 MRI 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 MRI contrast. Thus, IONPs@Asp-PTX-PEG-GSH are promising MRI-monitored paclitaxel (PTX) delivery vehicle across the BBB.