The hydroxyl dendrimers used in our platform rapidly distribute throughout the body after systemic administration, do not bind to tissues or proteins, are non-toxic, and are excreted intact in the urine.
The hydroxyl dendrimer is rapidly and selectively taken up in activated microglia. In a rabbit model of acute neonatal inflammation, systemic administration of the hydroxyl dendrimer containing a fluorescent label (Cy5) resulted in >95% of activated microglia taking up the dendrimer within 4 hours (Nance et al 2016; Zhang et al 2016). No significant uptake of the hydroxyl dendrimer occurred in other cells or in the healthy controls.
Preclinical studies in over 25 animal models have been conducted by the Company's Founders at Johns Hopkins University and, independently, by Orpheris. In all models activated microglia were present due to neuroinflammation, ischemia, infection or injury. As shown in the table below, hydroxyl dendrimers readily cross the blood brain barrier (BBB) in the presence of activated microglia regardless of the extent of neuroinflammation. The amount of hydroxyl dendrimer taken up in the brain is dependent on the severity of the neuroinflammation, which corresponds to the extent of microglial activation.