In vitro and in vivo studies on gelatin-siloxane nanoparticles conjugated with SynB peptide to increase drug delivery to the brain

Xin-hua Tian1, Feng Wei1, Tian-xiao Wang2, Peng Wang1, Xiao-ning Lin1, Jun Wang2, Dong Wang2, Lei Ren2,31Neurosurgical Department of Affiliated Zhongshan Hospital, 2Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, 3State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, People’s Republic of ChinaBackground: Nanobiotechnology can provide more efficient tools for diagnosis, targeted and personalized therapy, and increase the chances of brain tumor treatment being successful. Use of nanoparticles is a promising strategy for overcoming the blood–brain barrier and delivering drugs to the brain. Gelatin-siloxane (GS) nanoparticles modified with Tat peptide can enhance plasmid DNA transfection efficiency compared with a commercial reagent.Methods: SynB-PEG-GS nanoparticles are membrane-penetrable, and can cross the blood–brain barrier and deliver a drug to its target site in the brain. The efficiency of delivery was investigated in vivo and in vitro using brain capillary endothelial cells, a cocultured blood–brain barrier model, and a normal mouse model.Results: Our study demonstrated that both SynB-PEG-GS and PEG-GS nanoparticles had a spherical shape and an average diameter of 150–200 nm. It was shown by MTT assay that SynB-PEG-GS nanoparticles had good biocompatibility with brain capillary endothelial cells. Cellular uptake by SynB-PEG-GS nanoparticles was higher than that for PEG-GS nanoparticles for all incubation periods. The amount of SynB-PEG-GS nanoparticles crossing the cocultured blood–brain barrier model was significantly higher than that of PEG-GS nanoparticles at all time points measured (P <0.05). In animal testing, SynB-PEG-GS nanoparticle levels in the brain were significantly higher than those of PEG-GS nanoparticles at all time points measured (P < 0.01). In contrast with localization in the brain, PEG-GS