PEGlated magnetic polymeric liposome anchored with TAT for delivery of drugs across the blood-spinal cord barrier.

Abstract

Due to the existence of the blood-spinal cord barrier (BSCB), many therapeutic macromolecular agents, such as drugs, protein and gene, cannot pass through this barrier to reach the site of injury, all of which restricts the treatment of spinal cord injuries (SCI). In this study, TAT-conjugated PEGlated Magnetic polymeric liposomes (TAT-PEG-MPLs) formed from PEGlated amphiphilic octadecyl quaternized carboxymethyl chitosan (PEG-OQCMC), cholesterol (Chol), superparamagnetic nanoparticles, and transactivating-transduction protein (TAT), were prepared successfully and evaluated the properties in vitro and in vivo. The result indicated that TAT-PEG-MPLs were spherical in solution, with significantly small mean diameter (83.2 nm) and excellent magnetism (magnetization saturation values of 43.5 emu/g). In vitro experiment, the uptake of PEG-MPLs with TAT by MCF-7 cells was greater than that of the PEG-MPLs without TAT. Most importantly, in vivo experiment, a low MRI signal was observed in the T(2)-weighted images; Histological analysis, Cryo-TEM and flame atomic absorption spectrophotometry revealed that TAT-PEG-MPLs nanoparticles significantly accumulated around the site of the SCI even inside the nerve cells. These nanoparticles may provide a promising carrier to locate to the lesion site, deliver therapeutic macromolecular agents across the BSCB and penetrate into the nerve cells for the treatment of SCI.