Shock Wave Catheters for Intranasal Blood-Brain Barrier Bypass
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Solution Overview
Problem
Existing drug delivery methods for treating central nervous system diseases like Parkinson's disease, Alzheimer's disease, and epilepsy face challenges in evading the blood-brain barrier, leading to limited drug uptake due to factors such as first-pass metabolism, slow absorption, fast elimination, plasma protein binding, and adverse toxic effects on the periphery.
Innovation Solution
Utilizing intravascular lithotripsy devices to generate shock waves within the sinonasal cavity, bypassing the blood-brain barrier by delivering drugs coated on the surface of a catheter enclosure, which are ejected via shock waves to target the central nervous system through olfactory nerves.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional drug delivery methods are used, then drugs can be administered systemically, but the blood-brain barrier prevents effective drug uptake in the CNS
Solution Approach 1:
The patent uses shock waves as an intermediary mechanism to temporarily disrupt the blood-brain barrier. The shock waves travel through the nasal cavity tissue and across the BBB, creating transient openings that allow drug molecules to pass into the CNS. This mediator approach resolves the contradiction by providing a temporary pathway through the barrier without permanently damaging it.
Solution Approach 2:
The patent replaces conventional mechanical delivery methods (such as direct injection or surgical implantation) with acoustic shock wave technology. The shock waves use acoustic energy to mechanically disrupt the BBB and propel drugs through the tissue, substituting a non-invasive acoustic field for invasive mechanical procedures.
2Quantity of substance
If shock waves are used to disrupt the blood-brain barrier, then drug delivery is enhanced, but tissue damage may occur
Solution Approach 1:
The patent carefully controls parameters such as shock wave amplitude, frequency, and duration to optimize drug delivery while minimizing tissue damage. By adjusting these parameters, the shock waves create sufficient disruption in the BBB for drug passage without causing excessive damage to surrounding nasal cavity tissue. The conductive fluid also serves as a cushioning medium to reduce direct tissue impact.
Solution Approach 2:
The patent introduces a conductive fluid (such as saline) as a cushioning medium between the shock wave source and the tissue. This fluid absorbs and distributes the shock wave energy, preventing direct contact between the high-energy waves and the nasal cavity tissue, thereby reducing the risk of tissue damage while still enabling effective BBB disruption and drug delivery.
3Quantity of substance
If intranasal drug delivery is used, then the blood-brain barrier can be bypassed, but anatomical variations make consistent delivery difficult
Solution Approach 1:
The patent employs dynamic adjustment of shock wave parameters based on real-time feedback. The system can modify amplitude, frequency, and delivery duration adaptively to account for anatomical variations between patients. This dynamic approach allows consistent and effective drug delivery despite differences in nasal cavity anatomy, resolving the contradiction between bypassing the BBB and maintaining delivery consistency.
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
Enhances drug uptake in the CNS by precisely targeting and delivering therapeutically effective amounts of drugs beyond the blood-brain barrier, improving treatment efficacy for CNS diseases.
Implementation Method 1
The mechanism of plaque modification is through use of a catheter having one or more acoustic shock wave generating sources located within a liquid that can generate acoustic shock waves that modify the calcified plaque
Implementation Method 2
the energy creates one or more rapidly expanding and collapsing vapor bubbles that generate secondary shock waves
Implementation Method 3
For electrohydraulic generation of acoustic shock waves, a conductive solution (e.g., saline) may be contained within an enclosure that surrounds electrodes or can be flushed through a tube that surrounds the electrodes
Implementation Method 4
This absorption process rapidly heats and vaporizes the fluid, thereby generating the rapidly expanding and collapsing vapor bubble, as well as the acoustic shock waves
Implementation Method 5
Shock wave(s) generated by the one or more shock wave emitters impact the inner surface of the enclosure and cause the drug coated on the outer surface of the enclosure to be ejected from the outer surface
Data Source
AI summary
Described herein are shock wave catheters and methods of use thereof for delivering an active agent of a drug to the CNS via a body lumen or cavity, such as sinonasal cavity, which can bypass the blood-brain barrier (BBB). The catheters described herein can be advanced through an intranasal passage to the nasal cavity such that at least a portion of the enclosure is disposed in the nasal cavity. The enclosure can be coated with a drug coating. The method can include filling the enclosure with a conductive fluid. At least one shock wave can be generated at a shock wave emitter of the catheter disposed within the enclosure. The at least one shock wave can cause a therapeutically effective amount of the active agent of the drug coating to be delivered to the CNS via tissue of the nasal cavity, in turn, treating central nervous system diseases.