Polysaccharide cross-linked colloidal particles squeezable between internal body structures without aggregation, and use thereof as modifier for in vivo injection
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Solution Overview
Problem
Nanoparticles used for in vivo applications face challenges such as immune recognition, aggregation, and inefficient delivery to target sites due to interactions with extracellular matrix structures, leading to low therapeutic efficacy and potential toxicity.
Innovation Solution
Polysaccharide-crosslinked colloidal particles are engineered to be squeezable and dispersible within biological structures, with controlled physicochemical properties to evade immune recognition, enhance delivery, and regulate biodistribution and excretion, using intra- and inter-molecular crosslinking of polysaccharides at hydroxyl groups to form nanoparticles with specific surface functional groups.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nanoparticles are introduced into the body for in vivo applications, then unique optical, magnetic, and electrical properties can be utilized to observe and control biological processes, but the nanoparticles are recognized as foreign by the immune system and subject to phagocytosis, leading to accumulation in organs and difficulty in clearance
Solution Approach 1:
The patent uses polysaccharide-crosslinked colloidal particles as intermediary carriers to transport functional nanoparticles through the body. These colloidal particles serve as a mediator between the functional nanoparticles and the biological environment, providing biocompatibility and evading immune recognition while allowing the functional nanoparticles to perform their intended functions.
Solution Approach 2:
The invention creates composite structures by combining functional nanoparticles with polysaccharide-crosslinked colloidal particles. This composite approach allows the system to simultaneously exhibit the unique properties of the functional nanoparticles (optical, magnetic, electrical) while gaining the biocompatibility and immune-evasion capabilities of the polysaccharide matrix.
2Quantity of substance
If nanoparticles are used as drug delivery platforms with high surface-to-volume ratio, then a large number of drug molecules can be conjugated per unit mass, but the nanoparticles face difficulty in penetrating extracellular matrix structures and delivering drugs to target sites
Solution Approach 1:
The patent segments the drug delivery system into two functional components: polysaccharide-crosslinked colloidal particles for navigation and tissue penetration, and functional nanoparticles for high-capacity drug conjugation. This segmentation allows each component to optimize its specific function while working together as an integrated system.
Solution Approach 2:
The invention modifies the physicochemical parameters of the colloidal particles, including size distribution, surface charge, and crosslinking density, to optimize both drug loading capacity and tissue penetration ability. By carefully controlling these parameters, the system achieves high drug cargo while maintaining the ability to navigate through extracellular matrix structures.
3Reliability
If conventional nanoparticles are administered for targeted delivery to tumor tissues via the enhanced permeability and retention effect, then preferential penetration and accumulation can occur, but only approximately 0.7% of the injected dose is actually delivered to tumor tissue with less than 0.01% taken up by tumor cells
Solution Approach 1:
The polysaccharide-crosslinked colloidal particles act as intermediaries that facilitate the transport of functional nanoparticles from the bloodstream to the tumor tissue. These colloidal particles enhance the EPR effect by providing optimal size and surface properties for preferential accumulation in tumor tissues while improving cellular uptake efficiency.
Solution Approach 2:
The patent optimizes critical parameters including the size of colloidal particles (2-20 nm), surface charge characteristics, and crosslinking density to maximize both the EPR effect-mediated tissue accumulation and the subsequent cellular internalization efficiency, thereby significantly improving the fraction of injected dose that reaches tumor cells.
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 polysaccharide-crosslinked colloidal particles improve therapeutic delivery and efficacy by avoiding aggregation, prolonging circulation time, and enabling precise control over biodistribution and excretion, while maintaining biocompatibility and safety.
Implementation Method 1
a polysaccharide-crosslinked colloidal particle formed by intra- and/or inter-molecular crosslinking of 1 to 3 branched polysaccharides or 2 to 30 cyclic polysaccharides at hydroxyl groups of constituent monosaccharide building blocks using a crosslinker
Implementation Method 2
the polysaccharide-crosslinked colloidal particle and/or the in vivo administrable complex is engineered to be dispersible in vivo without aggregation
Implementation Method 3
a functional nanoparticle or a drug for in vivo administration, bound to a surface-exposed functional group derived from the crosslinker
Data Source
Figure 1a~1b
Figure 2
Figure 3a~3b
AI summary
The present invention relates to polysaccharide-crosslinked colloidal particles and their use as modifiers for substances intended for in vivo administration. The present invention provides a polysaccharide-crosslinked colloidal particle platform that is not only capable of serving as a drug delivery vehicle for functional nanoparticles or drugs intended for in vivo administration, but also can be engineered to regulate in vivo biodistribution and excretion.