Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy.

For medical emergencies, such as acute ischemic stroke, rapid drug delivery to the target site is essential. For many small molecule drugs, this goal is unachievable due to poor solubility that prevents intravenous administration, and less obviously, by extensive partitioning to plasma proteins and red blood cells (RBCs), which greatly slows delivery to the target. Here we study these effects and how they can be solved by loading into nanoscale drug carriers.

Post-Translational Chemical Modification of Amyloid-β Peptides by 4-Hydroxy-2-Nonenal.

Background: The extraction and quantification of amyloid-β (Aβ) peptides in brain tissue commonly uses formic acid (FA) to disaggregate Aβ fibrils. However, it is not clear whether FA can disaggregate post-translationally modified Aβ peptides, or whether it induces artifact by covalent modification during disaggregation. Of particular interest are Aβ peptides that have been covalently modified by 4-hydroxy-2-nonenal (HNE), an oxidative lipid degradation product produced in the vicinity of amyloid plaques that dramatically accelerates the aggregation of Aβ peptides.

Free Radical Chain Reactions and Polyunsaturated Fatty Acids in Brain Lipids.

Polyunsaturated fatty acyl chains (PUFAs) concentrate in the brain and give rise to numerous oxidative chemical degradation products. It is widely assumed that these products are the result of free radical chain reactions, and reactions of this type have been demonstrated in preparations where a single PUFA substrate species predominates. However, it is unclear whether such reactions can occur in the biologically complex milieu of lipid membranes where PUFA substrates are a minority species, and where diverse free radical scavengers or other quenching mechanisms are present.

Deuterated docosahexaenoic acid protects against oxidative stress and geographic atrophy-like retinal degeneration in a mouse model with iron overload.

Oxidative stress plays a central role in age-related macular degeneration (AMD). Iron, a potent generator of hydroxyl radicals through the Fenton reaction, has been implicated in AMD. One easily oxidized molecule is docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in photoreceptor membranes.