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

Background: 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 nanoparticle levels were significantly higher than those of SynB-PEG-GS nanoparticles (P < 0.01) in the liver.

Conclusion: This study indicates that SynB-PEG-GS nanoparticles have favorable properties with regard to morphology, size distribution, and toxicity. Moreover, the SynB-PEG-GS nanoparticles exhibited more efficient brain capillary endothelial cell uptake and improved crossing of the blood-brain barrier. Further, biodistribution studies of rhodamine-loaded nanoparticles demonstrated that modification with the SynB peptide could not only improve the ability of PEG-GS nanoparticles to evade capture in the reticuloendothelial system but also enhance their efficiency in crossing the blood-brain barrier.