Treatment of Parkinson's disease with biologics that penetrate the blood-brain barrier via receptor-mediated transport.

Parkinson's disease (PD) is characterized by neurodegeneration of nigral-striatal neurons in parallel with the formation of intra-neuronal α-synuclein aggregates, and these processes are exacerbated by neuro-inflammation. All 3 components of PD pathology are potentially treatable with biologics. Neurotrophins, such as glial derived neurotrophic factor or erythropoietin, can promote neural repair.

Receptor-mediated drug delivery of bispecific therapeutic antibodies through the blood-brain barrier.

Therapeutic antibody drug development is a rapidly growing sector of the pharmaceutical industry. However, antibody drug development for the brain is a technical challenge, and therapeutic antibodies for the central nervous system account for ~3% of all such agents. The principal obstacle to antibody drug development for brain or spinal cord is the lack of transport of large molecule biologics across the blood-brain barrier (BBB).

Brain gene therapy with Trojan horse lipid nanoparticles.

The COVID-19 mRNA vaccine was developed by the scalable manufacture of lipid nanoparticles (LNPs) that encapsulate mRNA within the lipid. There are many potential applications for this large nucleic acid delivery technology, including the delivery of plasmid DNA for gene therapy. However, gene therapy for the brain requires LNP delivery across the blood-brain barrier (BBB).

Physiologically Based Pharmacokinetic Model of Brain Delivery of Plasma Protein Bound Drugs.

Introduction: A physiologically based pharmacokinetic (PBPK) model is developed that focuses on the kinetic parameters of drug association and dissociation with albumin, alpha-1 acid glycoprotein (AGP), and brain tissue proteins, as well as drug permeability at the blood-brain barrier, drug metabolism, and brain blood flow.

Goal: The model evaluates the extent to which plasma protein-mediated uptake (PMU) of drugs by brain influences the concentration of free drug both within the brain capillary compartment in vivo and the brain compartment. The model also studies the effect of drug binding to brain tissue proteins on the concentration of free drug in brain.

Advanced Blood-Brain Barrier Drug Delivery.

This Special Issue of Pharmaceutics, "Advanced Blood-Brain Barrier Drug Delivery," comprises 16 articles or reviews, which cover a cross-section of brain drug delivery for either small-molecule or large-molecule therapeutics [...