Porous Hemoglobin Particles That Prevent Extravasation

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Solution Overview

Problem

Existing hemoglobin-based oxygen carriers (HBOCs) face safety concerns due to extravasation of cell-free hemoglobin, leading to vasoconstriction and oxidative tissue injury, and previous encapsulation methods like polymerization and liposome encapsulation compromise oxygen binding and release efficiency.

Innovation Solution

A method for producing matrix-encapsulated protein particles using a porous framework formed by combining framework precursors and proteins, followed by ultrafiltration to separate encapsulated and unencapsulated proteins, resulting in particles with high encapsulation efficiency and maintained oxygen binding capabilities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If Hb polymerization or surface conjugation is used to prevent extravasation, then safety is improved, but oxygen binding and release capability deteriorates

Engineering Contradiction:

ImprovesafetyVSAvoidoxygen binding and release capability

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent employs metal-organic frameworks (MOFs) with controlled porosity to encapsulate hemoglobin. The porous structure allows oxygen molecules to diffuse through to the encapsulated Hb while preventing Hb extravasation, thus maintaining oxygen binding capability while ensuring safety. The framework acts as a physical barrier that selectively permits gas exchange.

Inventive Principle:

Principle #31Porous materials

Solution Approach 2:

The patent implements nested encapsulation where hemoglobin is enclosed within MOF structures, which are themselves contained within liposome vesicles. This multi-layer nesting provides progressive protection: the MOF prevents Hb leakage while allowing O2 diffusion, and the liposome provides additional stabilization and biocompatibility, resolving the contradiction between preventing extravasation and maintaining function.

Inventive Principle:

Principle #7Nested doll (Nesting)

2Reliability

If liposome encapsulation is used to prevent extravasation, then safety is improved, but encapsulation efficiency deteriorates

Engineering Contradiction:

ImprovesafetyVSAvoidencapsulation efficiency

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent performs preliminary encapsulation of hemoglobin into metal-organic frameworks before liposome encapsulation. This pre-encapsulation step concentrates Hb into compact MOF particles with controlled size and structure, which then serve as discrete units for efficient liposome encapsulation. The preliminary structuring of Hb into MOFs facilitates higher encapsulation efficiency by providing defined targets for liposome uptake.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent creates composite structures combining MOFs and liposomes into hybrid nanoparticles. The composite material integrates the advantages of both components: MOFs provide high Hb loading capacity and structural stability, while liposomes provide biocompatibility and controlled release. This composite approach achieves both high encapsulation efficiency and improved safety.

Inventive Principle:

Principle #40Composite materials

3Reliability

If chemical modification of Hb is used to prevent extravasation, then safety is improved, but flexibility and cooperative oxygen binding deteriorates

Engineering Contradiction:

ImprovesafetyVSAvoidflexibility and cooperative oxygen binding

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent introduces metal-organic frameworks as an intermediary structure between hemoglobin and the external environment. The MOF acts as a mediator that physically protects Hb from chemical modification while allowing oxygen binding. The framework's porous structure permits O2 access to Hb without requiring chemical modification of Hb, thus preserving Hb flexibility and cooperative binding through the intermediary protection.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 produces particles with high encapsulation efficiency, preserving hemoglobin's biological activity and oxygen binding properties, addressing safety concerns and enhancing therapeutic potential.

Implementation Method 1

a population of metal-organic framework-encapsulated hemoglobin particles is formed by coordination of a metal salt and a ligand in the presence of hemoglobin

Methodology Applied

Scientific EffectMetal-organic framework formation: Metal Organic Framework

Implementation Method 2

separating the metal-organic framework-encapsulated hemoglobin from the reactant mixture using ultrafiltration

Methodology Applied

Scientific EffectUltrafiltration: Semipermeable Membrane

Data Source

PatentUS20250368757A1Particles comprising proteins encapsulated in a porous framework and methods of using thereof

Publication Date: 2025.12.04 OHIO STATE INNOVATION FOUND

AI summary

Disclosed are methods for producing matrix-encapsulated proteins, including matrix-encapsulated hemoglobin. Also provided are pharmaceutical compositions comprising a matrix-encapsulated hemoglobin, as well as methods of using thereof to treat hypoxia, cyanide poisoning, hydrogen sulfide poisoning, and/or azide poisoning.