Dextran-T10 Coated Iron Oxide Nanoparticles for MRI Contrast
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Solution Overview
Problem
There is an ongoing need for more reliable production methods for dextran-coated ultra-small superparamagnetic iron oxide nanoparticles with improved characteristics for use as MRI contrast agents, as existing methods face challenges in achieving consistent batch-to-batch variance and stability.
Innovation Solution
A method involving ultrafiltration of nanoparticles coated with dextran-T10, followed by adjusting the dextran-T10 content to 140-160 wt.% relative to iron, and optionally adding dextran-T1 and a tonicity agent like citrate to enhance stability and reliability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to produce dextran-coated iron oxide nanoparticles, then production is simpler, but batch-to-batch variance and stability are poor
Solution Approach 1:
The patent applies preliminary action by performing ultrafiltration before final formulation to pre-concentrate and pre-purify the nanoparticles. This preliminary step ensures consistent dextran coating and removes impurities that would cause batch variability, establishing a reliable foundation for subsequent steps.
Solution Approach 2:
The patent systematically changes critical parameters including dextran molecular weight (T10 specification), iron oxide particle size (5-10 nm), and dextran-to-iron weight ratio (140-160:100). These controlled parameter changes ensure reproducible coating thickness and particle characteristics across batches, directly improving reliability.
2Stability of the object's composition
If dextran coating is applied to iron oxide particles, then stability in circulation is improved, but achieving consistent dextran-to-iron ratio across batches becomes difficult
Solution Approach 1:
The patent implements feedback control by measuring the actual dextran-to-iron ratio in each batch and adjusting the formulation accordingly. Quality control measurements of dextran content and iron content allow real-time verification and correction, ensuring the ratio remains within the specified 140-160:100 range for optimal stability.
Solution Approach 2:
The patent specifies precise parameter ranges including dextran molecular weight (T10 with 10 kDa average), particle size (5-10 nm), and dextran-to-iron weight ratio (140-160:100). These controlled parameter changes ensure reproducible coating thickness and particle characteristics across batches.
3Reliability
If ultrafiltration and adjustment steps are added to the production method, then nanoparticle stability and consistency are improved, but production time and process complexity increase
Solution Approach 1:
The patent maintains continuity by performing ultrafiltration as a continuous process rather than batch processing, and by seamlessly transitioning between ultrafiltration, concentration, and formulation steps without interrupting the nanoparticle suspension. This continuous approach minimizes handling time and maintains particle stability throughout the process.
Solution Approach 2:
The patent combines multiple functions into integrated steps: ultrafiltration simultaneously concentrates the nanoparticles and removes impurities, while the subsequent formulation step combines concentration adjustment, dextran supplementation, and buffer addition in one operation, reducing overall process time.
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 method results in nanoparticles with improved stability and reduced batch-to-batch variance, maintaining a dispersion of at most 10% in dextran-T10 content, ensuring consistent performance and prolonged stability of the nanoparticles for use as effective MRI contrast agents.
Implementation Method 1
ultra-small superparamagnetic iron oxide nanoparticles coated with dextran-T10
Implementation Method 2
providing an ultrafiltrated composition comprising ultra-small superparamagnetic iron oxide nanoparticles coated with dextran-T10
Implementation Method 3
Dextran is an uncharged coating for the iron oxide particles and effectively stabilizes particle size in the vascular compartment
Implementation Method 4
ultra-small superparamagnetic iron oxide nanoparticles
Data Source
AI summary
The invention relates to a method for producing an adjusted nanoparticle composition comprising ultra-small superparamagnetic iron oxide nanoparticles coated with dextran-T10, compositions obtained thereby, and uses of such compositions. The adjusted compositions have improved parameters such as lower batch-to-batch variance and improved stability, and are useful as magnetic imaging agents.