Delivery of Biologics Across the Blood-Brain Barrier with Molecular Trojan Horse Technology.

Biologics are potential new therapeutics for many diseases of the central nervous system. Biologics include recombinant lysosomal enzymes, neurotrophins, decoy receptors, and therapeutic antibodies. These are large molecule drugs that do not cross the blood-brain barrier (BBB). All classes of biologics have been tested, without success, in clinical trials of brain disease over the last 25 years. In none of these past clinical trials was the biologic re-engineered to enable transport across the BBB. If the biologic does not cross the BBB, the drug cannot reach the target site in brain, and success in a clinical trial is not expected. Biologics can be re-engineered for BBB transport with the use of molecular Trojan horse technology. A BBB molecular Trojan horse is a monoclonal antibody (MAb) against an endogenous BBB receptor transporter, such as the insulin receptor or transferrin receptor. The receptor-specific MAb penetrates the brain via transport on the endogenous BBB receptor. The MAb acts as a molecular Trojan horse to deliver across the BBB the biologic pharmaceutical that is genetically fused to the MAb. The lead Trojan horse is a MAb against the human insulin receptor (HIR), and HIRMAb-derived fusion proteins have entered clinical trials for the treatment of brain disease.

A strategy for detecting absorbed bioactive compounds for quality control in the water extract of rhubarb by ultra performance liquid chromatography with photodiode array detector.

OBJECTIVE: To detect absorbed bioactive compounds of the water extract whose pharmacodynamic effect was craniocerebral protection for quality control assessment. METHODS: Anthraquinones in water extract of rhubarb (WER), in cerebrospinal fluid (CSF) of patients with traumatic brain injury (TBI) and in ipsilateral cortex of TBI rats following oral WER were respectively explored by ultra performance liquid chromatography with photodiode array detector (UPLC-PDA) method developed in the present study. The effects of anthraquinones absorbed into injured cortex on superoxidase dismutase (SOD) activity in TBI rats were detected. The antioxidative anthraquinones absorbed into target organ were evaluated for quality control of WER. RESULTS: Anthraquinones in WER were aloe-emodin, rhein, emodin, chrysophanol, and physcion. Only the last anthraquinone was found in CSF and in ipsilateral cortex under this chromatographic condition. Physcion increased SOD activity in TBI rats significantly. CONCLUSIONS: Physcion was the main active compound of rhubarb against craniocerebral injury via antioxidant pathway. According to our strategy, the exploration of physcion suggested the possibility of a novel quality control of WER in treating TBI injury.