Acoustically Responsive Microbubbles for Targeted Vasodilation

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Solution Overview

Problem

Current diagnostic and therapeutic tools for cardiovascular diseases, such as cardiovascular disease, cerebrovascular disease, and stroke, face challenges in effectively promoting vasodilation and delivering bioactive gases like nitric oxide, xenon, and hydrogen sulfide to target sites within the vasculature, due to rapid diffusion and degradation of these gases.

Innovation Solution

Development of acoustically responsive stabilized microbubbles with a phospholipid monolayer shell encapsulating bioactive gases in a specific volume ratio with perfluorocarbon gases, allowing for targeted and controlled release of these gases at diseased vasculature sites using ultrasound-mediated delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If bioactive gases like nitric oxide, xenon, and hydrogen sulfide are delivered to target sites within the vasculature, then therapeutic benefits for cardiovascular diseases are achieved, but the gases rapidly diffuse and degrade, reducing delivery effectiveness

Engineering Contradiction:

Improvedelivery effectivenessVSAvoidgas stability

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent uses a phospholipid monolayer shell to encapsulate bioactive gases, creating a flexible protective barrier that prevents rapid diffusion and degradation. The phospholipid shell maintains gas stability while allowing targeted delivery to vasculature, directly resolving the contradiction between delivery effectiveness and gas stability.

Inventive Principle:

Principle #30Flexible shells and thin films

Solution Approach 2:

The patent incorporates perfluorocarbon gases within the microbubble structure to create an inert internal environment that protects bioactive gases from degradation. This inert atmosphere extends the duration of gas action while maintaining reliable delivery to target sites.

Inventive Principle:

Principle #39Inert atmosphere (Inert environment)

2Measurement precision

If microbubbles are used as ultrasound contrast agents for imaging, then diagnostic capability is improved, but the microbubbles lack therapeutic functionality

Engineering Contradiction:

Improveimaging capabilityVSAvoidtherapeutic functionality

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent creates microbubbles that simultaneously serve diagnostic and therapeutic functions. The same phospholipid-encapsulated microbubbles used as ultrasound contrast agents also deliver bioactive gases for therapeutic vasodilation, eliminating the need for separate diagnostic and therapeutic interventions.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent merges diagnostic imaging capability with therapeutic gas delivery functionality into a single microbubble system. The microbubbles provide both ultrasound contrast for imaging and controlled release of bioactive gases for treatment, combining two previously separate functions into one unified platform.

Inventive Principle:

Principle #5Merging (Combining)

3Loss of information

If current imaging modalities are used to detect vulnerable atherosclerotic plaque, then diagnostic information is obtained, but the methods lack therapeutic capability and require separate treatment interventions

Engineering Contradiction:

Improvedisease detection accuracyVSAvoidtreatment protocol complexity

Core Design Contradiction:

Loss of informationVSDevice complexity

Solution Approach 1:

The patent employs microbubbles that function both as contrast agents for detecting vulnerable plaques and as vehicles for delivering therapeutic gases to the same target sites. This dual functionality eliminates the need for separate diagnostic and treatment protocols, reducing overall system complexity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 microbubbles provide both diagnostic and therapeutic benefits by maintaining bioactivity and stability of the gases, enabling effective vasodilation and treatment of cardiovascular diseases with improved delivery and reduced degradation, as demonstrated by their stability and bioactive gas loading capabilities.

Implementation Method 1

acoustically responsive stabilized microbubbles with a phospholipid monolayer shell encapsulating bioactive gases

Methodology Applied

Scientific EffectEncapsulation: Physical Containment

Implementation Method 2

acoustically responsive... allowing for targeted and controlled release of these gases at diseased vasculature sites using ultrasound-mediated delivery

Methodology Applied

Scientific EffectAcoustic cavitation: Acoustic Cavitation

Data Source

PatentUS11007284B2Gas-encapsulated acoustically responsive stabilized microbubbles and methods for treating cardiovascular disease

Publication Date: 2021.05.18 UNIVERSITY OF CINCINNATI

AI summary

Acoustically responsive stabilized microbubbles formulated with a phospholipid monolayer shell, an encapsulated bioactive gas, and an encapsulated perfluorocarbon gas of the formula CxFy in a volume ratio of from about 10:1 to about 1:10, wherein X is greater than or equal to 3, are disclosed. Also provided are methods for promoting localized vasodilation in a patient in need thereof by delivering a microbubble comprising a phospholipid monolayer shell and an encapsulated bioactive gas locally to a target diseased section of the patient's vasculature; and releasing the bioactive gas at the target diseased section, wherein the microbubble comprises the bioactive gas in a ratio of from about 10:1 to about 1:10 by volume with a perfluorocarbon gas.