Phosphorylated Polyol-Coated Metal Oxide Nanoparticles for Stable Aqueous Suspensions
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Solution Overview
Problem
Nanoparticles based on transition metal oxides, used for diagnostic imaging, often lack hydrophilicity, leading to instability in aqueous suspensions and polydisperse particle size distributions, which complicates their use as effective contrast agents in medical imaging applications.
Innovation Solution
A nanoparticle composition comprising a nanoparticulate metal oxide core coated with a phosphorylated polyol, featuring at least two phosphate groups in a 1,2 or 1,3 spatial relationship, and hydrophilic groups like polyethylene ether moieties, which enhances hydrophilicity and stability in aqueous suspensions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If transition metal oxide nanoparticles are used for diagnostic imaging, then imaging properties are improved, but hydrophilicity is insufficient leading to poor suspension stability
Solution Approach 1:
The surface chemistry parameters of the nanoparticle are changed by introducing phosphate groups and polyethylene ether moieties. This modifies the hydrophilicity parameter of the metal oxide surface, transforming it from hydrophobic to hydrophilic, thereby enabling stable aqueous suspension without agglomeration or precipitation
Solution Approach 2:
The patent creates a composite surface structure on the metal oxide nanoparticle by combining phosphate groups with polyethylene ether moieties. This composite material approach integrates the surface binding capability of phosphate groups with the hydrophilic properties of polyethylene ether, achieving both stable attachment to the metal oxide surface and excellent aqueous compatibility
2Reliability
If surface treatments are applied to enhance hydrophilicity, then aqueous stability is improved, but particle size distribution becomes polydisperse
Solution Approach 1:
The patent applies surface treatment during the nanoparticle synthesis process itself, rather than as a subsequent step. The phosphate groups and polyethylene ether moieties are introduced concurrently with nanoparticle formation, ensuring uniform distribution and consistent particle size throughout the population, thereby maintaining monodispersity while achieving hydrophilicity
3Reliability
If purification techniques are employed to prepare formulations, then formulation quality is improved, but hydrophilicity and particle size distribution are degraded
Solution Approach 1:
The nanoparticle surface is designed to be self-stabilizing through the inherent hydrophilic properties of the phosphate-polyethylene ether composite structure. This self-service capability allows the particles to maintain their suspension stability and hydrophilicity throughout purification processes without requiring additional protective measures or experiencing degradation
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 nanoparticle composition forms stable aqueous colloidal suspensions with no significant change in hydrodynamic diameter over time, ensuring robust suspension stability and improved safety for in vivo use as a diagnostic agent.
Implementation Method 1
stabilizer substances are thought to attach to the surface of the suspended nanoparticulate core species and to form a barrier (or shell) interposed between at least a portion of the surface of the nanoparticulate core species and the diluent
Implementation Method 2
a phosphorylated polyol comprising at least two phosphate groups... wherein at least two of the phosphate groups occupy positions in the phosphorylated polyol which constitute a 1,2 or 1,3 spatial relationship to one another
Implementation Method 3
the polyol comprises a hydrophilic group selected from the group consisting of polyethylene ether moieties, polypropylene ether moieties, polybutylene ether moieties
Data Source
AI summary
A diagnostic agent composition is provided which comprises a nanoparticle composition and a pharmaceutically acceptable carrier or excipient. The nanoparticle composition comprises a nanoparticulate metal oxide and a phosphorylated polyol, wherein the phosphorylated polyol comprises at least two phosphate groups and one or more hydrophilic groups selected from the group consisting of polyethylene ether moieties, polypropylene ether moieties, polybutylene ether moieties, and combinations of two or more of the foregoing hydrophilic moieties. The disclosure provides detailed guidance on methods of making and using such diagnostic agent compositions. The diagnostic agent compositions provided by the present invention are useful as contrast agents for medical diagnostic imaging techniques such as magnetic resonance (MR) imaging and X-ray imaging. The diagnostic agent composition may be administered to a subject via a variety of techniques, among them injection, inhalation, and ingestion.