Disulfide Crosslinked Protein Nanoparticles for IBD Delivery
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Solution Overview
Problem
Current therapies for inflammatory bowel disease (IBD) face challenges due to the harsh environment of the gastrointestinal tract, which limits the effectiveness of biologics and leads to systemic immunosuppression and toxicity, necessitating improved delivery methods for therapeutic agents.
Innovation Solution
Development of nanoparticles comprising recombinant proteins, such as AvrA, with disulfide bonds for crosslinking, which are designed to withstand the gastrointestinal environment and target specific sites for enhanced therapeutic delivery and bioactivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If biologics are administered orally or by injection to treat IBD, then therapeutic effect is achieved, but the biologics cannot survive serum proteases, harsh gastrointestinal environment, or clearance processes leading to reduced effectiveness
Solution Approach 1:
The patent uses nanoparticles as intermediary carriers to protect biologics from the harsh gastrointestinal environment. The nanoparticle carrier shields the biologic from serum proteases and clearance processes, enabling oral or injectable administration while maintaining therapeutic effectiveness in IBD treatment.
Solution Approach 2:
The patent employs disulfide crosslinking to modify the structural parameters of nanoparticles, creating a stable configuration that withstands gastrointestinal conditions. The disulfide bonds provide structural integrity while allowing controlled disassembly in the reducing environment of the gut, thereby protecting and delivering biologics effectively.
2Object-affected harmful factors
If current IBD therapies use systemic corticosteroids and immunosuppressants, then inflammation is suppressed, but systemic immunosuppression and toxicities occur
Solution Approach 1:
The patent enables localized delivery of therapeutic proteins to the intestinal tract through nanoparticle formulation. This local delivery approach concentrates the therapeutic effect at the site of inflammation while minimizing systemic exposure, thereby reducing systemic immunosuppression and toxicities associated with conventional IBD therapies.
3Stability of the object's composition
If nanoparticles are designed to withstand gastrointestinal environment, then stability is improved, but the complexity of maintaining stability and bioactivity increases
Solution Approach 1:
The patent creates composite nanoparticle structures combining proteins with disulfide crosslinkers. This composite approach provides inherent stability in gastrointestinal conditions through the crosslinked network while maintaining bioactivity, avoiding the need for complex protective coatings or additional stabilizing agents.
Solution Approach 2:
The patent utilizes the redox parameter change between the oxidizing gastrointestinal environment and the reducing intracellular environment to control nanoparticle stability and disassembly. Disulfide crosslinks remain intact in the gut but break in the reducing environment, providing automatic stability control without complex design interventions.
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 nanoparticles effectively deliver therapeutic proteins to the intestinal tract, reducing inflammation and improving symptoms in IBD models by suppressing pro-inflammatory signaling, while maintaining stability and bioactivity in the harsh gastrointestinal conditions.
Implementation Method 1
particles comprising recombinant proteins, such as AvrA, with disulfide bonds for crosslinking
Implementation Method 2
The nanoparticles effectively deliver therapeutic proteins to the intestinal tract
Implementation Method 3
reducing inflammation and improving symptoms in IBD models by suppressing pro-inflammatory signaling
Data Source
Figure 1~2C
Figure 3A~3D
Figure 4A~5
AI summary
This disclosure relates to particles comprising recombinant proteins, pharmaceutical composition comprising the particles, and therapeutic uses related thereto. In certain embodiments, the particles are made by the process of producing recombinant proteins and conjugating the recombinant proteins to form nanoparticles with a linking reagent comprising disulfide bonds. Typically the recombinant protein has a polypeptide of viral, fungal, or bacterial origin such as secreted effector proteins AvrA and YopJ. In certain embodiments, the disclosure relates to treating or preventing autoimmune diseases, cancer, or inflammatory diseases, or conditions such as inflammatory bowel disease (IBD).