Hydrogel Drug Delivery via Anti-PEG Antibody Binding

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Solution Overview

Problem

Delivering therapeutic agents to the brain for treating conditions such as brain tumors is challenging due to the blood-brain barrier and the invasive nature of local injections, which can lead to complications.

Innovation Solution

A hydrogel-based drug delivery system embedded with anti-PEG antibodies, which binds to polyethylene glycol (PEG)-conjugated therapeutic agents, allowing for targeted delivery to the brain by attracting and retaining the agents within the brain tissue.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If therapeutic agents are delivered systemically, then the treatment can reach the brain, but the blood-brain barrier blocks the agents from entering the brain

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidblood-brain barrier blocking

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses an antibody-PEG conjugate as an intermediary mechanism. The antibody component recognizes and binds to PEGylated therapeutic agents in the bloodstream, facilitating their transport across the blood-brain barrier through receptor-mediated transcytosis. This intermediary binding mechanism allows systemic delivery to overcome the barrier without direct penetration.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the therapeutic agent by conjugating it with polyethylene glycol (PEG), which changes its physical and chemical parameters. This PEGylation alters the agent's size, hydrophilicity, and recognition properties, enabling it to be captured by antibodies and transported across the blood-brain barrier more effectively.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If local injection is used to deliver therapeutic agents into the intracranial space, then the agents can reach the brain, but frequent injections cause complications

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidinjection complications

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent employs a preliminary action by pre-conjugating the therapeutic agent with PEG and pre-positioning antibodies at the injection site or on the surface of brain tissue. This preparation allows a single systemic administration to be retained and released over time, reducing the frequency of injections required.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent achieves continuous therapeutic action through sustained release mechanisms. The therapeutic agent is delivered once systemically and then retained at the brain site through antibody binding or hydrogel encapsulation, providing continuous exposure without requiring repeated injections. This extends the duration of action from hours to days or weeks.

Inventive Principle:

Principle #20Continuity of useful action

3Loss of time

If the drug delivery system is administered only once, then the treatment frequency is reduced, but the retention of therapeutic agents in the brain must be maintained

Engineering Contradiction:

Improvetreatment frequencyVSAvoidagent retention time

Core Design Contradiction:

Loss of timeVSDuration of action of stationary object

Solution Approach 1:

The patent ensures continuous useful action through sustained release mechanisms. The therapeutic agent is delivered once systemically and then retained at the brain site through antibody binding or hydrogel encapsulation, providing continuous exposure without requiring repeated injections. This extends the duration of action from hours to days or weeks.

Inventive Principle:

Principle #20Continuity of useful action

Solution Approach 2:

The patent employs recoverable binding mechanisms where antibodies bound to PEGylated agents can be recycled. As agents are released from the blood, antibodies continuously capture and retain them at the brain site, effectively recovering and reusing the binding capacity to maintain therapeutic levels over extended periods.

Inventive Principle:

Principle #34Discarding and recovering

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 system enhances the delivery efficiency and retention of therapeutic agents in the brain, effectively treating brain disorders like glioma with reduced need for frequent injections and minimizing complications.

Implementation Method 1

The antibody binds polyethylene glycol (PEG)

Methodology Applied

Scientific EffectAntibody-antigen binding:

Implementation Method 2

hydrogel-based drug delivery system

Methodology Applied

Scientific EffectDiffusion: Diffusion

Implementation Method 3

one or more biodegradable polymers (e.g., hyaluronic acid molecules)

Methodology Applied

Scientific EffectBiodegradation: Decomposition (biological)

Data Source

PatentUS11382983B2Reloadable hydrogel system for treating brain conditions

Publication Date: 2022.07.12 ACAD SINICA

AI summary

A drug delivery system and methods of using such for delivering a peglyated therapeutic agent to brain. The drug delivery system may comprise an antibody, which binds polyethylene glycol (PEG), wherein the antibody is embedded in a hydrogel, which may comprises one or more biodegradable polymers, up to 60% of which contain inter-chain or intra-chain covalent crosslinks. The amount of the antibody in the drug delivery system can be about 1-2 μg per μl of the hydrogel.