DDEL-33. NEO100 facilitates delivery of blood-brain barrier impenetrable drugs

Abstract The blood-brain barrier (BBB) is a selective, protective barrier that serves to shield the brain from harmful substances while regulating transport of essential molecules. While this barrier is crucial for maintaining the brain’s homeostasis, it presents a significant challenge for drug delivery, particularly for treating central nervous system (CNS) disorders. Many therapeutic agents, especially large or hydrophilic molecules, are unable to cross the BBB effectively. This includes a wide range of antibiotics, anticancer agents, monoclonal antibodies, and most biologics. Even small molecule drugs can be actively pumped out by efflux transporters like P-glycoprotein, reducing their CNS bioavailability. Consequently, numerous potentially effective drugs fail to reach therapeutic concentrations in the brain. This limitation has major implications for treating brain malignancies, such as glioma. For example, the chemotherapy drug doxorubicin, while effective against many cancers, is largely excluded from the brain due to the BBB. To overcome this obstacle, we have investigated the potential of intra-nasal co-administration of therapeutic drugs with NEO100 (a highly pure, pharmaceutical-grade form of the natural monoterpene perillyl alcohol) to enhance brain delivery through direct nose-to-brain transport. We have shown that NEO100 significantly enhances the brain tumor specific uptake and retention of doxorubicin, dexamethasone, and remdesivir when administered via an intra-nasal route in a formulation that contains NEO100 at concentrations as low as 1%, when compared to traditional oral or IV routes of administration. The evaluation of both drugs alone and in the presence of NEO100 was performed by quantitative HPLC analysis at time points ranging from 15 minutes to 24 hours post administration. Understanding how NEO100 functions in manipulating the barrier’s physiology is crucial for developing next-generation therapeutics capable of treating CNS diseases effectively. Continued innovation in drug design and delivery technologies is essential for expanding the range of treatable neurological conditions