Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives.

Due to their high specificity, monoclonal antibodies have been widely investigated for their application in drug delivery to the central nervous system (CNS) for the treatment of neurological diseases such as stroke, Alzheimer's, and Parkinson's disease. Research in the past few decades has revealed that one of the biggest challenges in the development of antibodies for drug delivery to the CNS is the presence of blood-brain barrier (BBB), which acts to restrict drug delivery and contributes to the limited uptake (0.1-0.2% of injected dose) of circulating antibodies into the brain. This article reviews the various methods currently used for antibody delivery to the CNS at the preclinical stage of development and the underlying mechanisms of BBB penetration. It also describes efforts to improve or modulate the physicochemical and biochemical properties of antibodies (e.g., charge, Fc receptor binding affinity, and target affinity), to adapt their pharmacokinetics (PK), and to influence their distribution and disposition into the brain. Finally, a distinction is made between approaches that seek to modify BBB permeability and those that use a physiological approach or antibody engineering to increase uptake in the CNS. Although there are currently inherent difficulties in developing safe and efficacious antibodies that will cross the BBB, the future prospects of brain-targeted delivery of antibody-based agents are believed to be excellent.

Upgrading Biodiesel from Vegetable Oils by Hydrogen Transfer to its Fatty Esters.

Conversion of vegetable-derived triglycerides to fatty acid methyl esters (FAMEs) is a popular approach to the generation of biodiesel fuels and the basis of a growing industry. Drawbacks of the strategy are that (a) the glycerol backbone of the triglyceride is discarded as waste, and (2) most available natural triglycerides in the U.S. are multi-unsaturated or fully saturated, giving inferior fuel performance and causing engine problems. Here we show that catalysis by iridium complex 1 can address both of these problems through selective reduction of triglycerides high in polyunsaturation. This is realized using hydrogen from methanol or those imbedded in the triglyceride backbone, concurrently generating lactate as a value-added C3 product. Additional methanol or glycerol as a hydrogen source enables reduction of corn and soybean oils to > 80% oleate. The cost of the iridium catalyst is mitigated by its recovery through aqueous extraction. The process can be further driven with a supporting iron-based catalyst for the complete saturation of all olefins. Preparative procedures are established for synthesis and separation of methyl esters of the hydrogenated fatty acids, enabling instant access to upgraded biofuels.