Solid Lipid Nanoparticles for ICG Photostability and Blood Half-Life
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Indocyanine Green (ICG) suffers from rapid metabolic clearance, instability in aqueous solutions, and lack of target specificity, limiting its clinical applications in fluorescence imaging, particularly for tumor detection and lymph node mapping due to its short blood residence time and aggregation issues.
Innovation Solution
Formulating ICG into solid lipid nanoparticles (SLNs) with a solid lipid core, amphiphilic components, and a stabilizing alkaline-earth complex, which enhances photostability, prolongs blood circulation, and improves fluorescence signal through the EPR effect and steric constraints.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If ICG is administered intravenously at the clinical recommended dose, then it provides rapid hepatobiliary excretion and short blood half-time, but it lacks significant targeting property at tumor tissue and has low efficiency in in vivo imaging
Solution Approach 1:
The patent combines ICG with solid lipid nanoparticles to create a composite formulation. The SLN carrier provides prolonged blood circulation and tumor targeting capability through the EPR effect, while ICG provides fluorescence imaging function. This composite structure resolves the contradiction by maintaining the fluorescence properties of ICG while adding the targeting and prolonged circulation properties of SLNs.
Solution Approach 2:
The solid lipid nanoparticle acts as an intermediary carrier between the bloodstream and tumor tissue. It mediates the delivery of ICG to tumor sites by exploiting the EPR effect, thereby providing targeting capability that free ICG lacks. The SLN intermediary enables prolonged blood residence time while directing accumulation at tumor tissue.
2Quantity of substance
If ICG is used in aqueous solution, then it provides fluorescence imaging capability, but it aggregates and loses stability within 6 hours
Solution Approach 1:
The solid lipid nanoparticle forms a protective shell around the ICG molecule. This lipid shell isolates ICG from the aqueous environment, preventing aggregation while maintaining fluorescence properties. The amphiphilic nature of the lipid forms a stable interface that keeps ICG dispersed and stable in aqueous solution for extended periods.
Solution Approach 2:
The patent changes the physical state of the lipid from liquid to solid, creating solid lipid nanoparticles. This phase change provides structural rigidity and enhanced stability to the nanoparticle formulation, preventing ICG aggregation and maintaining formulation stability over time compared to liquid lipid emulsions.
3Stability of the object's composition
If polymeric nanoparticles are used to improve aqueous stability of ICG, then half-life in aqueous solution increases to 2.5-3 days, but fluorescence intensity decreases and particle size increases to around 350 nm
Solution Approach 1:
The patent changes the lipid phase from liquid to solid, creating SLNs with a solid core. This provides a more rigid and stable structure that maintains smaller particle size compared to polymeric nanoparticles. The solid lipid matrix also provides a favorable environment for ICG fluorescence while maintaining aqueous stability, avoiding the fluorescence quenching observed with polymeric carriers.
4Stability of the object's composition
If nanoemulsion is used for ICG, then it provides improved stability, but the core should remain amorphous which complicates formulation and may favor expulsion of encapsulated molecules
Solution Approach 1:
The patent utilizes the phase transition of lipids from liquid to solid to create a stable core structure. By using solid lipids with defined melting points above body temperature, the formulation achieves a crystalline or semi-crystalline core that is more stable than amorphous structures. This phase transition approach simplifies formulation by providing a well-defined structural state rather than requiring amorphous maintenance.
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 SLN formulation achieves prolonged blood circulation, enhanced photostability, and improved fluorescence quantum yield, allowing for effective tumor targeting and imaging, with the nanoparticles maintaining stability and fluorescence efficiency over time.
Implementation Method 1
The SLN formulation achieves prolonged blood circulation, enhanced photostability, and improved fluorescence quantum yield, allowing for effective tumor targeting and imaging
Implementation Method 2
Formulating ICG into solid lipid nanoparticles (SLNs) with a solid lipid core, amphiphilic components, and a stabilizing alkaline-earth complex
Implementation Method 3
improves fluorescence signal through the EPR effect and steric constraints
Implementation Method 4
a fluorescent dye of the cyanine family and/or a polyheterocyclic compound selected from: coumarin, pyrano, quinoline, pyranoquinoline, indole and pyranoindole derivatives
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention discloses a solid lipid nanoparticle (SLN) comprising: a) a solid lipid core comprising at least a glyceride and/or at least a fatty acid; b) a mixture of amphiphilic components forming a shell around said core a); c) an alkaline-earth complex with a compound of formula I and/or II: d) at least a fluorescent dye selected from: a cyanine fluorescent dye and /or a polyetherocyclic compound selected from: coumarin, pyrano, quinoline, pyranoquinoline, indole and pyranoindole derivates in acid form or a pharmaceutically acceptable salt thereof. These nanoparticles allow a prolonged blood circulation half-life, show enhanced photostability and improved fluorescence signal. The dye is preserved from degradation and improves the fluorescent quantum yield.