Alternating Electric Fields for Blood-Brain Barrier Permeability
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Solution Overview
Problem
The blood-brain barrier (BBB) restricts the diffusion of large or hydrophilic drug molecules, preventing their delivery to the brain for treating diseases.
Innovation Solution
Applying an alternating electric field to the brain at specific frequencies and durations increases the permeability of the BBB, allowing substances to cross and be administered after the field application.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If the BBB operates normally to prevent harmful substances from entering the brain, then protection of the brain is improved, but delivery of large or hydrophilic drug molecules to the brain is blocked
Solution Approach 1:
The patent applies alternating electric fields to dynamically modulate the BBB permeability. The electric field parameters (frequency, amplitude, duration) can be adjusted to temporarily increase permeability for drug delivery, then reduced to restore normal barrier function, making the BBB's permeability property dynamic rather than static
Solution Approach 2:
The patent uses periodic application of alternating electric fields to temporarily open the BBB. The fields are applied in cycles with specific frequencies (e.g., 1-100 kHz) and durations, creating periodic windows of increased permeability that allow drug molecules to cross while maintaining overall barrier integrity between cycles
2Reliability
If the BBB restricts diffusion of large or hydrophilic molecules to protect the brain, then brain protection is improved, but therapeutic drug delivery is worsened
Solution Approach 1:
The patent applies alternating electric fields before drug administration to pre-condition the BBB. By temporarily increasing permeability in advance, the barrier is prepared to allow subsequent drug molecule passage, while the preliminary field application does not permanently compromise barrier integrity
Solution Approach 2:
The patent changes physical parameters of the BBB environment by applying alternating electric fields with specific frequencies and amplitudes. These parameter changes temporarily alter tight junction properties to increase permeability, enabling drug delivery without permanently changing the barrier's protective function
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
The method temporarily enhances BBB permeability, enabling the delivery of molecules up to 69 kDa across the barrier, facilitating treatment of brain diseases and diagnostics.
Implementation Method 1
By linking to the actin cytoskeleton, these proteins form a strong cell-cell connection. Application of the alternating electric field to the subject's brain for the period of time increases permeability of the blood brain barrier
Data Source
AI summary
Certain substances (e.g., large molecules) that ordinarily cannot traverse the blood brain barrier can be introduced into the brain by applying an alternating electric field to the brain for a period of time, wherein the frequency of the alternating electric field is selected so that application of the alternating electric field increases permeability of the blood brain barrier. In some embodiments, the frequency of the alternating electric field is less than 190 kHz (e.g., 100 kHz). Once the permeability of the blood brain barrier has been increased, the substance is able to cross the blood brain barrier.