Compositions and methods for removing bio-synthetic nano-particles from bodily fluids
Inventors
Pan, Dipanjan • Doctor, Allan • Mittal, Nivesh
Assignees
Kalocyte Inc • University of Maryland Baltimore • University of Maryland Baltimore County UMBC
Publication Number
US-12161765-B2
Publication Date
2024-12-10
Expiration Date
2042-03-11
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Abstract
Bait and capture methods and compositions for removing bio-synthetic nano-particles from body fluids. Bio-synthetic nano-particles are baited with one-half of a bait and capture complex and lyophilized. The baited bio-synthetic nano-particle is reconstituted and administered to a subject for diagnostic or therapeutic purposes. To remove the bio-synthetic nano-particle from the body, the body fluid containing the baited bio-synthetic nano-article is contacted with the capture portion of the bait and capture complex. The body fluid from which the bio-synthetic nano-particles have been removed may be returned to the subject.
Core Innovation
The invention provides bait and capture methods and compositions for the efficient and selective removal of bio-synthetic nano-particles, such as artificial oxygen carriers, from bodily fluids. The core of this approach is a supramolecular assembly technique that utilizes a host-guest interaction between an adamantane (“ADM”) tag on the nano-particle and a β-cyclodextrin (β-CD) functionalized polystyrene (PS) bead as the capture agent. The nano-particles are first tagged with the adamantane compound, lyophilized for storage and transport, then reconstituted and administered to a subject.
The problem addressed by the invention is the interference of bio-synthetic nano-particles, specifically ErythroMer (EM), with clinical laboratory analyses, including complete blood count and metabolic panels, due to their color and light-scattering properties in blood samples. Traditional strategies do not effectively remove these nanoparticles, leading to inaccurate diagnostic results and complications in patient care. There is an urgent clinical need for a selective and robust method to eliminate such nano-particles from blood specimens.
According to the invention, after administration of the adamantane-tagged nano-particle, bodily fluid containing the nano-particle is contacted with mono-6-O-(p-toluenesulfonyl)-β-cyclodextrin functionalized PS beads. The strong affinity between adamantane and β-cyclodextrin enables the capture and removal of the tagged nano-particles from the fluid. This allows for the return of purified body fluid to the subject or for laboratory analysis without interference from the nanoparticles.
Claims Coverage
There is one independent claim, outlining the primary inventive features of the invention.
Removal of adamantane-tagged nano-particles from bodily fluid using β-cyclodextrin functionalized polystyrene beads
The method involves: 1. Complexing an adamantane compound to a nano-particle. 2. Administering the adamantane-tagged nano-particle to a subject. 3. Subsequently contacting the bodily fluid with mono-6-O-(p-toluenesulfonyl)-β-cyclodextrin functionalized polystyrene beads. 4. This process results in removal of the adamantane-tagged nano-particle from the bodily fluid. The adamantane compound has a specified formula, and the method is applicable to nanoparticles administered for diagnostic or therapeutic use.
The inventive feature centers on a unique bait (adamantane) and capture (β-cyclodextrin on polystyrene beads) system for removing nano-particles from bodily fluids through highly selective supramolecular chemistry.
Stated Advantages
Facile formation of the inclusion complex between adamantane and β-cyclodextrin under ambient conditions, allowing pilot-scale studies without special genetic or biochemical techniques.
The small molecular adamantane tag has little to no effect on nano-particle structure and function.
Optimal β-cyclodextrin functionalization on polystyrene beads introduces insignificant changes to column bead pore size, enabling safe blood stream clearance.
The method efficiently and selectively removes synthetic nano-particles, resolving interference in clinical laboratory blood analyses.
Both bait and capture components are compatible with scalable packaging, storage, and commercial manufacturing.
Documented Applications
Removal of ErythroMer and other bio-synthetic nano-particles from whole blood or blood specimens for clinical laboratory analyses.
Use in hemoperfusion cartridges for removing tagged ErythroMer from the bloodstream in living patients via extracorporeal circuits such as dialysis systems and CPB systems.
Removal of tagged ErythroMer from perfusate in ex vivo organ or organoid preparations.
Packaging of lyophilized bait-tagged ErythroMer in pre-filled tubes or containers for reconstitution at the site of use.
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