Bi-Phasic Microbubble Clusters for Low-Power Ultrasound Drug Delivery

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Solution Overview

Problem

Existing ultrasound-mediated drug delivery technologies face limitations such as low drug loading capacity, high acoustic power requirements, rapid washout of microbubbles, and safety concerns like micro-haemorrhage and irreversible vascular damage, hindering clinical transition.

Innovation Solution

A bi-phasic microbubble/microdroplet formulation where microbubbles are physically attached to emulsion microdroplets prior to administration, forming stable clusters that undergo a liquid-to-gas transition at low ultrasound power, producing large activated bubbles for targeted drug delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If microbubbles are used for drug delivery, then localized delivery to pathology is improved, but rapid washout occurs reducing duration of action

Engineering Contradiction:

Improvedrug loading capacityVSAvoidretention time in vasculature

Core Design Contradiction:

Quantity of substanceVSDuration of action of moving object

Solution Approach 1:

The patent combines microbubbles with microdroplets to form cluster compositions. The microdroplets serve as a reservoir that slowly releases drug-containing material, thereby extending the retention time in vasculature while maintaining the localized delivery capability of microbubbles. This merging resolves the contradiction between achieving high drug loading and preventing rapid washout.

Inventive Principle:

Principle #5Merging (Combining)

2Productivity

If high acoustic power is used to activate microbubbles, then drug release is improved, but harmful bio-effects increase

Engineering Contradiction:

Improvedrug release efficiencyVSAvoidmicro-haemorrhage and vascular damage

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the physical-chemical parameters of the delivery system by incorporating microdroplets with specific surface tension properties and shell compositions. These parameter changes enable the system to be activated at lower acoustic power levels, improving drug release efficiency while reducing harmful bio-effects such as micro-haemorrhage and irreversible vascular damage.

Inventive Principle:

Principle #35Parameter changes

3Quantity of substance

If microbubbles are used for drug delivery, then localized delivery is improved, but safety concerns arise due to cavitation mechanisms

Engineering Contradiction:

Improvelocal drug concentrationVSAvoidcavitation-induced damage

Core Design Contradiction:

Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent creates a composite material system combining microbubbles and microdroplets with different functional properties. The microdroplet component provides a safer activation mechanism that reduces cavitation-induced damage while the microbubble component maintains the ability to achieve high local drug concentration at the target site. This composite approach resolves the safety contradiction.

Inventive Principle:

Principle #40Composite materials

4Quantity of substance

If ultrasound energy is increased to overcome skull bone, then blood brain barrier delivery is improved, but thermal effects and damage increase

Engineering Contradiction:

Improvedrug delivery across blood brain barrierVSAvoidthermal effects from ultrasound

Core Design Contradiction:

Quantity of substanceVSTemperature

Solution Approach 1:

The patent changes the activation parameters of the delivery system by using microdroplets with tuned surface tension and shell properties. These parameter changes allow the system to be activated at lower ultrasound energy levels, improving drug delivery across the blood brain barrier while minimizing thermal effects and tissue damage from excessive ultrasound exposure.

Inventive Principle:

Principle #35Parameter changes

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

This approach significantly increases drug loading capacity, avoids rapid washout, reduces acoustic power needs, and minimizes bio-effects, enabling efficient and safe drug delivery to target tissues.

Implementation Method 1

a bi-phasic microparticle system comprising gas microbubbles, emulsion microdroplets and clusters thereof

Methodology Applied

Scientific EffectElectrostatic attraction: Electrostatics

Implementation Method 2

Application of ultrasound oscillates microbubbles present in the microcirculation and induce well-established mechanisms that increase the local permeability of the vasculature, allowing drugs to diffuse at an increased rate into the tissue space

Methodology Applied

Scientific EffectSonoporation: Acoustic Cavitation

Implementation Method 3

forming stable clusters that undergo a liquid-to-gas transition at low ultrasound power, producing large activated bubbles for targeted drug delivery

Methodology Applied

Scientific EffectPhase transition (liquid-to-gas): Phase Change

Data Source

PatentUS20260027211A1Ultrasound mediated delivery of drugs

Publication Date: 2026.01.29 EXACT THERAPEUTICS AS

AI summary

The present invention relates to ultrasound (US) mediated delivery of therapeutic agents, such as the delivery of a drug, gene, nanoparticle or radioisotope, using a bi-phasic microparticle system comprising gas microbubbles, emulsion microdroplets and clusters thereof. Thus, the present invention relates to a cluster composition and a pharmaceutical composition, and their use for delivery of therapeutic agents and as a contrast agent for ultrasound imaging. It further relates to methods for delivering such therapeutic agents and to the use of said compositions.