Polyphosphazene Nanoclusters for Renal Excretion
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Solution Overview
Problem
Current X-ray contrast agents, particularly iodinated small molecules, pose a risk of acute kidney injury due to high concentrations in the kidneys, and existing nanoparticles either retain in the body for long periods or are excreted too quickly, limiting their clinical application.
Innovation Solution
Development of nanoclusters comprising biocompatible and biodegradable polyphosphazene-encapsulated inorganic nanocrystals, which can be renally excreted, allowing for controlled release and reduced nephrotoxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If nanoparticles larger than 5 nm are used, then long circulation times and accumulation in diseased tissues are achieved, but long-term retention in the body occurs preventing swift urinary excretion
Solution Approach 1:
The patent segments the nanoparticle into two functional components: a large core (≥5 nm) providing long circulation time and a small excretable shell (<5 nm) enabling renal clearance. This segmentation allows the particle to exhibit both long circulation characteristics and rapid excretion capabilities by separating the functional requirements into different size regimes.
Solution Approach 2:
The patent employs a nested structure where smaller excretable nanoparticles are embedded within or attached to larger circulating nanoparticles. The smaller particles serve as 'seeds' that can be released and excreted via kidneys, while the larger structure provides prolonged circulation and targeting capabilities, creating a hierarchical size architecture.
2Loss of substance
If smaller nanoparticles smaller than 5 nm are used, then swift excretion via kidneys is achieved, but long circulation times and accumulation in diseased tissues are lost
Solution Approach 1:
The patent merges the advantages of small particles (rapid renal excretion) with large particles (long circulation) by combining them into a single hybrid nanoparticle system. The small excretable units are integrated within or on the surface of larger circulating carriers, allowing the system to simultaneously achieve both fast clearance and prolonged vascular residence time.
Solution Approach 2:
The patent creates a composite nanoparticle system combining materials or structures with different size characteristics. The composite architecture includes both sub-5 nm excretable components and larger circulating components, leveraging the complementary properties of each size regime to achieve optimized pharmacokinetics with both long circulation and rapid excretion.
3Illumination intensity
If iodinated contrast agents are used, then effective X-ray contrast is achieved, but risk of acute kidney injury and contrast-induced nephropathy increases
Solution Approach 1:
The patent uses biocompatible polymers and surfactants as intermediary materials to replace toxic iodinated contrast agents. These intermediary substances provide the necessary X-ray attenuation properties while being non-nephrotoxic, serving as safe mediators between the imaging requirement and kidney safety constraints.
Solution Approach 2:
The patent changes the fundamental parameter of contrast agent composition from iodine-based small molecules to nanoparticle-based heavy metal cores (such as gold, bismuth, or barium) with polymer coatings. This parameter change maintains high X-ray attenuation capability while eliminating the nephrotoxicity associated with iodinated compounds, particularly for patients with renal insufficiency.
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 nanoclusters provide effective contrast for imaging while minimizing kidney burden, with controlled excretion and biocompatibility, enhancing safety for patients with renal insufficiency.
Implementation Method 1
Nanoparticles made of heavy elements such as iodine, gold, bismuth, or platinum attenuate X-rays strongly
Implementation Method 2
nanoclusters comprising inorganic nanocrystals and a biocompatible and biodegradable polymer
Data Source
AI summary
Nanoclusters comprising inorganic nanocrystals and a biodegradable polymer are disclosed. The inorganic nanocrystals have a mean particle size of 1 to 500 nm. The inorganic nanocrystals are contained within a core of the nanoclusters, on the surface of the nanoclusters, contained within a core of the nanoclusters, dispersed throughout the nanoclusters, or a combination thereof. The biodegradable polymer allows the inorganic nanocrystals to be excreted renally over a period of time. The nanoclusters can be used for medical imaging or other biomedical applications.