HPG-Coated Core-Shell Particles for Stealth and Tissue Adhesion
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Solution Overview
Problem
Existing nanoparticle coatings, particularly those using polyethylene glycol (PEG), face challenges in achieving optimal stealth or adhesive properties and efficient targeting, leading to rapid clearance and limited delivery to non-liver targets due to non-specific protein adsorption and MPS uptake.
Innovation Solution
Development of hyperbranched polyglycerol-coated nanoparticles (HPG NPs) with tunable coatings that can be modified to resist non-specific protein absorption (stealth properties) or promote adhesion (bioadhesive properties) through chemical modifications of hydroxyl groups, allowing for the attachment of targeting moieties and encapsulation of therapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If PEG is used as nanoparticle coating to provide stealth properties, then non-specific protein adsorption is reduced, but adhesive properties and targeting capability are compromised
Solution Approach 1:
The patent uses a composite coating system combining PEG (for stealth properties) with hyperbranched polyglycerol (for adhesive properties and targeting capability). This composite approach allows the nanoparticle surface to simultaneously achieve protein resistance and tissue adhesion, resolving the contradiction between stealth and adhesive properties.
Solution Approach 2:
The patent applies different functional groups at different locations or regions of the nanoparticle surface. The PEG provides stealth properties in certain regions while the hyperbranched polyglycerol with its hydroxyl groups provides adhesive properties in other regions, allowing localized functional optimization.
2Duration of action of moving object
If PEG coating is used to increase blood circulation, then clearance is reduced, but delivery to non-liver targets is limited due to MPS uptake
Solution Approach 1:
The composite coating of PEG and hyperbranched polyglycerol provides both extended blood circulation (via PEG's stealth properties) and improved delivery to non-liver targets (via the adhesive properties of hyperbranched polyglycerol that prevent MPS uptake), thus resolving the contradiction between circulation time and delivery reliability.
Solution Approach 2:
The patent modifies the surface chemistry parameters of the nanoparticle coating by incorporating hydroxyl groups from hyperbranched polyglycerol alongside PEG. This parameter change in surface chemistry allows the coating to maintain stealth properties while adding adhesive characteristics that prevent MPS recognition and uptake.
3Object-affected harmful factors
If PEG chains are densely packed on nanoparticle surface, then stealth properties are enhanced, but achieving optimal density becomes difficult
Solution Approach 1:
The patent uses hyperbranched polyglycerol as a complementary material to PEG. The hyperbranched structure provides a different packing architecture that facilitates optimal surface density more easily than PEG alone, while maintaining protein adsorption resistance through the composite effect.
Solution Approach 2:
The patent creates a non-uniform surface structure where PEG and hyperbranched polyglycerol are distributed to provide different local functions. The hyperbranched polyglycerol regions provide adhesive properties and facilitate targeting, while PEG regions provide stealth properties, with the combined structure achieving optimal overall density.
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
Enhances nanoparticle circulation time, improves targeting specificity, and facilitates effective delivery of therapeutic agents to desired tissues by resisting MPS uptake and promoting tissue adhesion, thereby overcoming limitations of PEG coatings.
Implementation Method 1
The HPG coating can be modified to adjust the properties of the particles. For example, unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood.
Implementation Method 2
Alternatively, the hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups on tissue or otherwise interact with tissue to adhere the particles to the tissue, cells, or extracellular materials, such as proteins.
Implementation Method 3
The HPG can be covalently bound to the one or more materials that form the core such that, upon self-assembly, particles are formed in which the hydrophobic or more hydrophobic materials form the core and the HPG forms a coating on the particle.
Data Source
AI summary
Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.