Intranasal Delivery: A Direct Path to the Brain
Intranasal delivery offers significant advantages over systemic options like IV or oral methods. This non-invasive technique, recognized for its Central Nervous System (CNS) applications since 1991, provides rapid onset with fewer side effects.
This method uniquely bypasses the circulatory system, using olfactory and trigeminal nerve pathways to deliver therapeutics directly to the brain’s Cerebrospinal Fluid (CSF). Small molecule aerosols can thus reach targeted disease sites, bypassing the Blood-Brain Barrier (BBB), which ensures rapid onset and minimizes systemic side effects.
NeOnc’s studies validate our proprietary POH formulations (standalone or combinatorial) for CNS treatment. Intranasal delivery of NEO100 consistently shows faster delivery and significantly higher uptake into the CSF and brain tissue, indicating a strong positive impact on disease treatment.
Intra-Arterial Delivery: NeOnc's Enhanced Approach
Intra-arterial delivery uses a catheter, often via an external port or implanted pump, to deliver therapeutics directly into an arterial passageway or the spinal cord. This method provides direct access to the Cerebrospinal Fluid (CSF), minimizing systemic impact and bypassing the Blood-Brain Barrier (BBB). Traditionally used for pain management, recent efforts explore its use for delivering chemotherapeutics to treat gliomas.
NeOnc’s Chairman and CEO, Dr. Thomas Chen, has been instrumental in this advancement, developing one of the first smart, implantable pumps for the metronomic delivery of chemotherapeutics. This innovation underscores the potential for more precise and effective CNS disease treatment.
When treating brain-based diseases such as gliomas, intra-arterial delivery still has the same issue as traditional delivery methods: how to transport the therapeutic past the BBB. Though an arterial or spinal cord catheter can deliver a drug into a cerebral passageway, and in the case of the spinal cord catheter directly into the CSF, the BBB will restrict drug delivery into the brain tissue.
NeOnc’s POH formulations can potentially overcome this hurdle by conjugating the therapeutic into a small molecule lipophilic structure, which can pass through the tight junction of the BBB’s endothelial cells.
For intra-arterial delivery, a catheter is fed through the tumor-feeding artery to the tumor site. The POH-based agent is then injected, allowing it to be absorbed through the BBB directly into the tumor. This essentially creates a temporary, targeted opening through the BBB for highly concentrated drug delivery. After treatment, the catheter is withdrawn, and the BBB naturally re-seals without harming healthy tissue.
Conjugated Delivery: NeOnc's Advanced Approach
NeOnc’s research suggests our proprietary NEO100 (POH) formulation offers a unique advantage: its ability to be conjugated with other therapeutics, forming a new drug like NEO212 (NEO100 + Temozolomide). This process potentially imbues the partner drug with NEO100’s transport capabilities, crucially without losing therapeutic efficacy. This conjugated approach opens significant opportunities for more effective brain cancer treatments, particularly for Glioblastoma Multiforme.
Current IV and oral administrations face major hurdles: systemic dilution, and the Blood-Brain Barrier (BBB). Large or hydrophilic molecules, including many chemotherapeutics like Temozolomide (TMZ), struggle to pass the BBB’s tight junctions into cerebral tissue. However, our research indicates POH’s small, lipophilic structure allows it to pass.
When TMZ is conjugated with NeOnc’s proprietary POH formulation, POH’s solvent nature appears to alter TMZ’s structure, enabling its unaffected passage into brain tissue. This represents a leap forward, allowing pharma-based therapeutics to be delivered directly to the brain, potentially lowering side effects associated with high systemic dosing.