Gelatin-ICG Complex Suppressing Contrast Agent Leakage

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Solution Overview

Problem

Indocyanine green (ICG) used as a contrast agent for photoacoustic tomography and fluorescent imaging has stability issues due to leakage and degradation when used in water-based formulations, leading to decreased molar absorption coefficients and ineffective imaging.

Innovation Solution

A gelatin-ICG complex is formed by covalently bonding phospholipids or cholesterol to gelatin, creating a stable complex that suppresses ICG leakage through noncovalent interactions, maintaining high molar absorption coefficients and preventing degradation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ICG is used as a contrast agent in water-based formulations, then it can be administered and distributed in the body, but it leaks and degrades over time, resulting in decreased molar absorption coefficient and reduced imaging effectiveness

Engineering Contradiction:

Improvestability of ICGVSAvoidleakage of ICG

Core Design Contradiction:

ReliabilityVSLoss of substance

Solution Approach 1:

ICG is encapsulated within gelatin particles, creating a nested structure where the contrast agent is contained inside a protective carrier. This nesting prevents ICG from directly contacting water, thereby preventing leakage and degradation while maintaining its imaging functionality.

Inventive Principle:

Principle #7Nested doll (Nesting)

Solution Approach 2:

The invention creates a composite material system combining gelatin (a biocompatible polymer) with ICG (a contrast agent). The gelatin-ICG complex forms a stable composite where gelatin provides structural integrity and protection, while ICG provides the desired optical properties for imaging.

Inventive Principle:

Principle #40Composite materials

2Stability of the object's composition

If ICG is encapsulated in PLGA particles to prevent degradation, then stability is improved, but ICG still leaks from the particles into surrounding water, causing discoloration and reduced effectiveness

Engineering Contradiction:

Improvestability of ICG-containing particleVSAvoidleakage of ICG from particle

Core Design Contradiction:

Stability of the object's compositionVSLoss of substance

Solution Approach 1:

The invention changes the material parameter of the encapsulating carrier from PLGA (a synthetic polymer with known leakage issues) to gelatin (a natural polymer with different physical and chemical properties). This parameter change results in a carrier that better retains ICG while maintaining biocompatibility.

Inventive Principle:

Principle #35Parameter changes

3Ease of operation

If ICG is dissolved in water inside liposomes, then it can be delivered to target sites, but ICG degrades rapidly or leaks from the liposome, resulting in discoloration and reduced imaging quality

Engineering Contradiction:

Improvedeliverability of ICGVSAvoidstability of ICG in liposome

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The invention changes the carrier material parameter from liposome (phospholipid bilayer structure) to gelatin particles (protein-based matrix). This parameter change creates a more stable environment for ICG, preventing both rapid degradation and leakage while maintaining deliverability to target sites.

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

The gelatin-ICG complex maintains high molar absorption coefficients and stability over time, enhancing photoacoustic signal intensity and fluorescence imaging, particularly in near-infrared wavelengths, and effectively targets tumor sites via the enhanced permeability and retention effect.

Implementation Method 1

The gelatin-ICG complex can suppress leakage of ICG from the complex by an interaction between a phospholipid or a cholesterol covalently bonded to gelatin and ICG.

Methodology Applied

Scientific EffectNoncovalent interaction: Van der Waals Force

Implementation Method 2

ICG sufficiently absorbs a light in the near-infrared wavelength range, which has little influence on the irradiated human body and is highly permeable in a living body

Methodology Applied

Scientific EffectLight absorption: Absorption (EM radiation)

Implementation Method 3

ICG emits fluorescence when excited by a light in the near-infrared wavelength range

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Implementation Method 4

effectively targets tumor sites via the enhanced permeability and retention effect

Methodology Applied

Scientific EffectEnhanced permeability and retention effect:

Data Source

PatentUS9132203B2Complex and contrast agent for photoimaging using the same

Publication Date: 2015.09.15 CANON KK

AI summary

There is provided a gelatin-ICG complex that can suppress leakage of ICG included therein. The complex has a gelatin derivative including at least one of a phospholipid covalently bonded to a gelatin or a cholesterol covalently bonded to a gelatin, and indocyanine green.