Paramagnetic Solid Lipid Nanoparticles for MRI Contrast Agents
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Solution Overview
Problem
Current MRI contrast agents based on nanoparticles face challenges such as high accumulation in non-target organs like the liver and spleen, leading to prolonged exposure to toxic gadolinium and instability, which limits their clinical use and safety.
Innovation Solution
Development of paramagnetic solid lipid nanoparticles (pSLNs) using amphiphilic chelating agents like diazepine and tetraazacyclododecane derivatives, which are designed to enhance gadolinium payload and relaxivity, while minimizing accumulation in reticuloendothelial organs and improving stability through a solid lipid core.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional nanoparticles are used as MRI contrast agents, then gadolinium payload and relaxivity are improved, but accumulation in reticuloendothelial organs increases leading to toxicity
Solution Approach 1:
The patent changes the physical state of the lipid core from liquid to solid, which fundamentally alters the nanoparticle's interaction with reticuloendothelial cells. This phase change reduces cellular uptake and accumulation in the liver and spleen, thereby decreasing gadolinium accumulation and associated toxicity while maintaining high relaxivity values
Solution Approach 2:
The patent creates a composite structure combining solid lipid core with amphiphilic chelating agents that have both hydrophilic and hydrophobic portions. This composite approach allows the hydrophobic portion to interact with the solid lipid core while the hydrophilic portion faces outward, creating a stable structure with high gadolinium payload that avoids reticuloendothelial accumulation
2Quantity of substance
If conventional nanoparticles are used as MRI contrast agents, then relaxivity is improved, but stability deteriorates
Solution Approach 1:
The patent utilizes the phase transition of lipids from liquid to solid state to create a rigid, stable core structure. This solid lipid core provides structural integrity and prevents nanoparticle degradation, thereby improving stability while maintaining the high relaxivity achieved through amphiphilic chelating agents
3Quantity of substance
If conventional nanoparticles are used as MRI contrast agents, then gadolinium payload is improved, but harmful effects increase
Solution Approach 1:
By changing the lipid core to solid state, the patent reduces the nanoparticle's recognition and uptake by reticuloendothelial cells, thereby decreasing gadolinium accumulation in the liver and spleen and reducing toxic exposure while maintaining high gadolinium payload in the nanoparticle structure
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 pSLNs achieve higher relaxivity values, allowing for lower doses of gadolinium, reduced toxicity, and improved biodistribution, with enhanced stability and safety profiles, enabling effective MRI imaging with reduced exposure to toxic ions.
Implementation Method 1
paramagnetic metal ions chelating agents such as tetraaza-cyclododecanes and diazepine-derivatives for use as contrast agents in MRI (Magnetic Resonance Imaging)
Implementation Method 2
improving stability through a solid lipid core
Implementation Method 3
enhance gadolinium payload and relaxivity
Data Source
AI summary
The present invention relates to paramagnetic solid lipid nanoparticles (pSLNs) comprising an amphiphilic paramagnetic metal chelating moiety selected from: a diazepine derivative of Formula I and a tetraazocyclododecane derivative of Formula (II): being said chelating moiety complexed to a paramagnetic metal ion selected from the group consisting of: Gd(III), Mn(II), Cr(III), Cu(II), Fe(III), Pr(III), Nd(III), Sm(III), Tb(III), Yb(III), Dy(III), Ho(III) and Er(III), or salts thereof. The invention further relates to the process for preparation of said solid lipid nanoparticles comprising amphiphilic complexes of paramagnetic metals (pSLNs) and to the use of pSLNs as MRI contrast agents in the diagnostic field.