Polysaccharide Related to the Cause of Fungal Meningitis Temporarily Breaks Down Blood-Brain Barrier, Suggesting Effective Delivery of Therapeutics
This major capsular polysaccharide of the fungus Cryptococcus neoformans (C. neoformans), glucuronoxylomannan (GXM), can be administered with or attached to a drug to temporarily enable it to cross the blood-brain barrier for delivery to the central nervous system. C. neoformans is an opportunistic pathogenic yeast that produces capsular glucuronoxylomannan (GXM) during infection, typically in people with compromised immune systems. The glucuronoxylomannan accumulates in the body and contributes to the virulence of C. neoformans, the most common cause of fungal meningitis, which causes an estimated 200,000 deaths worldwide per year. Glucuronoxylomannan (GXM) interacts with the blood brain barrier, a protective structure that regulates movement of particles into the central nervous system, compromising the balance of fluids, immune cells, and other vital factors to maintain the central nervous system. These findings should be considered in the development of therapeutics.
Researchers at the University of Florida have discovered glucuronoxylomannan (GXM) can enable drug delivery across the blood-brain barrier to the central nervous system temporarily. By administering the polysaccharide in mice, researchers demonstrated how glucuronoxylomannan (GXM) causes rapid structural changes in the blood-brain barrier, including weakening of tight junction proteins and disruption of human brain endothelial cells interactions.
Application
Capsular polysaccharide temporarily disrupts the blood-brain barrier to deliver drugs simply and effectively to the central nervous system
Advantages
- Temporarily increases the permeability of the blood-brain barrier, improving the delivery of drugs to the central nervous system
- Can be co-administered or attached to drugs, making delivery to the central nervous system simple and effective
Technology
University of Florida researchers have discovered glucuronoxylomannan (GXM), the major capsular polysaccharide of Cryptococcus neoformans (C. neoformans), temporarily increases the permeability of the blood-brain barrier and allows drug delivery to the central nervous system. C. neoformans infects the central nervous system by inhalation and travels from the lungs to the bloodstream and crosses to the brain via transcytosis, paracytosis, or inside of phagocytes via a “Trojan horse” mechanism. Glucuronoxylomannan (GXM) disrupts tight junction and adhesion proteins and the trans-endothelial electrical resistance, which destabilizes the blood-brain barrier and promotes passage of C. neoformans into the desired location. Cell cultures and in vivo tests using mice support these findings.
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