Intranasal administration of gold nanoparticles designed to target the central nervous system: Fabrication and comparison between nanospheres and nanoprisms.

The presence of the blood-brain barrier (BBB) limit gold nanoparticles (GNP) accumulation in central nervous system (CNS) after intravenous (IV) administration. The intranasal (IN) route has been suggested as a good strategy for circumventing the BBB. In this report, we used gold nanoprisms (78 nm) and nanospheres (47 nm), of comparable surface areas (8000 vs 7235 nm2) functionalized with a polyethylene glycol (PEG) and D1 peptide (GNPr-D1 and GNS-D1, respectively) to evaluate their delivery to the CNS after IN administration. Cell viability assay showed that GNPr-D1 and GNS-D1 were not cytotoxic at concentrations ranged between 0.05 and 0.5 nM. IN administration of GNPr-D1 and GNS-D1 demonstrated a significant difference between the two types of GNP, in which the latter reached the CNS in higher levels. Pharmacokinetic study showed that the peak brain level of gold was 0.75 h after IN administration of GNS-D1. After IN and IV administrations of GNS-D1, gold concentrations found in brain were 55 times higher via the IN route compared to IV administration. Data revealed that the IN route is more effective for targeting gold to the brain than IV administration. Finally, no significant difference was observed between the IN and IV routes in the distribution of GNS-D1 in the various brain areas.

Reactions of the transient species Cr(CO)5(cyclohexane) with C4HnE (n=4, 8; E=O, NH, S) studied by time-resolved IR absorption spectroscopy.

Time-resolved IR absorption spectroscopy is used to investigate substitution of the cyclohexane (CyH) molecule of the photolytically generated alkane-solvated transient intermediate Cr(CO)5(CyH) by heterocyclic ligands C4HnE (n=4, 8; E=O, NH, S). From the concentration and temperature dependences of the pseudo-first order rate constants, we obtain activation parameters for the reactions, and find that they are consistent with an associative (A) or interchange (I) mechanism. As was the case with ligand substitution reactions at W(CO)5(CyH), a ligand's reactivity depends both on its electron-donating ability and on its polarizability. We also find that for a reaction with a given DeltaH, the activation entropy is higher for reaction of Cr(CO)5(CyH) than it is for reaction of W(CO)5(CyH). Comparison of the present results with ligand substitution reactions of W(CO)5(CyH), CpMn(CO)2(CyH), and Cr(CO)5(n-heptane) indicates that for ligand substitution reactions at alkane-solvated transition-metal intermediates, the solvent's effect upon the reaction rate is primarily entropic.