The blood-brain barrier (BBB) is vital for maintaining brain homeostasis by enabling an exquisite control of exchange of compounds between the blood and the brain parenchyma. Moreover, the BBB prevents unwanted toxins and pathogens from entering the brain. This barrier, however, breaks down with age and further disruption is a hallmark of many age-related disorders. Several drugs have been explored, thus far, to protect or restore BBB function. With the recent connection between the BBB and gut microbiota, microbial-derived metabolites have been explored for their capabilities to protect and restore BBB physiology. This review, will focus on the vital components that make up the BBB, dissect levels of disruption of the barrier, and discuss current drugs and therapeutics that maintain barrier integrity and the recent discoveries of effects microbial-derived metabolites have on BBB physiology.

Au nanoparticles with diameters ranging between 15 and 170 nm have been synthesised in aqueous solution using a seed-mediated growth method, employing hydroxylamine hydrochloride as a reducing agent. Thiolated polyethylene glycol (mPEG-SH) polymers, with molecular weights ranging from 2100 to 51 000 g mol⁻¹, were used as efficient particle stabilising ligands. Dynamic light scattering and zeta potential measurements confirmed that the overall mean diameter and zeta potential of the capped nanoparticles increased in a non-linear way with increasing molecular weight of the mPEG-SH ligand. Electron microscopy and thermal gravimetric analysis of the polymer-capped nanoparticles, with a mean gold core diameter of 15 nm, revealed that the grafting density of the mPEG-SH ligands decreased from 3.93 to 0.31 PEG nm⁻² as the molecular weight of the ligands increased from 2100 to 51 400 g mol⁻¹ respectively, due to increased steric hindrance and polymer conformational entropy with increase in the PEG chain length. Additionally, the number of bound mPEG-SH ligands, with a molecular weight of 10 800 g mol⁻¹, was found to increase in a non-linear way from 278 (σ = 42) to approximately 12 960 PEG (σ = 1227) when the mean Au core diameter increased from 15 to 115 nm respectively. However, the grafting density of mPEG_10 000-SH ligands was higher on 15 nm Au nanoparticles and decreased slightly from 1.57 to 0.8 PEG nm⁻² when the diameter increased; this effect can be attributed to the fact that smaller particles offer higher surface curvature, therefore allowing increased polymer loading per nm². Au nanoparticles were also shown to interact with CT-26 cells without causing noticeable toxicity.