Real-time imaging of a rodent brain shows that nanoparticles coated with polyethylene-glycol (PEG) (green) penetrate farther within the brain than particles without the PEG coating (red). Credit: Elizabeth Nance, Graeme Woodworth, Kurt Sailor
Targeted drug delivery by ferrying nanoparticles is a major field of research, promising highly effective therapies for all kinds of diseases while limiting side effects. The brain has been particularly interesting for this research, as it’s an organ that’s evolved all kinds of defense strategies – from the scalp to the blood brain barrier – making it difficult to work on, directly.
The brain’s extracellular space (ECS) is a network of channels that form between cells within which an ionic fluid transports nutrients, signaling molecules, and other chemicals throughout the brain. The narrow channels of the ECS limit the size of the particles that can move through, a problem that has put serious brakes on the use of nano-therapies in the brain.
Johns Hopkins University scientists have good news though, having discovered that by coating nanoparticles with polyethylene glycol (PEG) they were able to pass ones through the ECS nearly twice as big as before. It seems that beside the narrowness of the channels, there’s also a mechanism that makes particles stick to the walls. A dense coating of PEG helps the particles glide through, which the team demonstrated in mouse brains by moving 114 nm particles through the ECS, a significant improvement over previously used 64nm particles.
More from the study abstract:
Using these minimally adhesive PEG-coated particles, we estimated that human brain tissue ECS has some pores larger than 200 nm and that more than one-quarter of all pores are ≥100 nm. These findings were confirmed in vivo in mice, where 40- and 100-nm, but not 200-nm, nanoparticles spread rapidly within brain tissue, only if densely coated with PEG. Similar results were observed in rat brain tissue with paclitaxel-loaded biodegradable nanoparticles of similar size (85 nm) and surface properties. The ability to achieve brain penetration with larger nanoparticles is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find use in the treatment of brain tumors, stroke, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible.
Press release: Improved Nanoparticles Deliver Drugs Into Brain
Study abstract in Science Translational Medicine: A Dense Poly(Ethylene Glycol) Coating Improves Penetration of Large Polymeric Nanoparticles Within Brain Tissue
