Olfactory Delivery Scaffold Linkers for Blood-Brain Barrier Bypass
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Solution Overview
Problem
Existing methods for delivering therapeutic components to the brain are hindered by the blood-brain barrier, limiting effective treatment of neurological and neurodegenerative diseases.
Innovation Solution
Olfactory delivery scaffolds that utilize an olfactory targeting component, a therapeutic component, and a linker, which are cleaved by nasal enzymes to bypass the blood-brain barrier, enabling intracellular and transcellular transport to the brain.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic components are delivered through conventional routes (systemic circulation), then the blood-brain barrier prevents effective delivery to the brain, but alternative routes increase device complexity and administration difficulty
Solution Approach 1:
The patent employs the olfactory system as an intermediary pathway between the nasal cavity and the brain. The olfactory epithelium serves as a natural mediator that facilitates transport of therapeutic components across the cribriform plate into the olfactory bulb and subsequently to the brain, bypassing the blood-brain barrier without requiring complex delivery devices
Solution Approach 2:
The invention extracts and utilizes the natural olfactory transport pathway that exists independently of the blood-brain barrier. By taking advantage of this pre-existing biological route, the patent eliminates the need for complex engineered delivery systems while achieving reliable brain delivery
2Productivity
If the olfactory delivery scaffold uses multiple transport mechanisms (intracellular, paracellular, transcellular), then delivery efficiency to the brain is improved, but the molecular structure complexity increases
Solution Approach 1:
The olfactory delivery scaffold is designed with multi-functional capabilities to utilize multiple transport mechanisms simultaneously. The scaffold can undergo intracellular transport via endocytosis, paracellular transport through tight junctions, and transcellular transport through the olfactory epithelium, making it universally adaptable to different biological pathways and significantly enhancing delivery efficiency
Solution Approach 2:
The scaffold employs a composite molecular structure combining hydrophilic and hydrophobic regions, along with specific functional groups that enable interaction with different biological membranes and transport mechanisms. This composite design allows the single molecular entity to engage with multiple transport pathways concurrently
3Reliability
If enzymes in nasal mucus cleave the linker component to release the therapeutic component, then targeted delivery to the brain is achieved, but the therapeutic component may be degraded before reaching the target
Solution Approach 1:
The linker component is designed with enzyme-cleavable bonds that are specifically targeted by nasal mucus enzymes. This preliminary design ensures that the therapeutic component is released only after the scaffold has successfully navigated to the olfactory epithelium and been processed by nasal enzymes, preventing premature degradation and ensuring targeted delivery
Solution Approach 2:
The patent converts the potential harm of enzyme-mediated degradation into a beneficial release mechanism. By designing the linker to be specifically cleaved by nasal mucus enzymes, the system transforms what could be a degradation problem into a controlled release advantage, ensuring the therapeutic component is liberated at the correct location and time
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Delivers therapeutic components directly to the brain, effectively treating neurological and neurodegenerative diseases such as Parkinson's and Alzheimer's without systemic absorption.
Implementation Method 1
it is cleaved by enzymes (e.g., esterase, amidase, nuclease, and/or hydrolase) present in the nasal mucus into an olfactory targeting component and a separate therapeutic component
Implementation Method 2
This pathway is established by olfactory epithelium that use intracellular, paracellular, and/or transcellular transport of molecules and/or particles via, for example, endocytosis into olfactory sensory neurons
Data Source
AI summary
Exemplary olfactory delivery scaffolds may include 1) an olfactory targeting component, stimulant, or odorant that is recognized by the olfactory nerves via, for example, a smell response, 2) a molecule with biological activity, a therapeutic component, and/or drug (sometimes collectively referred to herein as a “therapeutic component”), and 3) a linker component that links the olfactory targeting component and therapeutic component together. The olfactory delivery scaffolds may be used to deliver a molecule with biological activity and/or a therapeutic component to a subject's neurological system through the olfactory pathway and pharmaceutical compositions useful in the treatment of neurological and/or neurodegenerative diseases.