Block Copolymer Nanoparticles for Blood-Brain Barrier Delivery

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Solution Overview

Problem

The blood-brain barrier (BBB) poses a significant challenge for the delivery of therapeutic agents to the central nervous system (CNS), as it restricts the entry of substances due to tight junctions, enzymatic activity, and efflux systems, making it difficult for exogenously administered drugs and peptides to cross and reach neurological disorders effectively.

Innovation Solution

A pharmaceutical composition comprising a complex of a therapeutic polypeptide and a synthetic block copolymer with a core-shell morphology, where the block copolymer self-assembles into nanoparticles, allowing for site-specific and sustained delivery across the BBB, utilizing a polyion segment with a charge opposite to the polypeptide, which forms stable complexes that can be administered with immune cells to target the CNS.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional drug delivery methods are used, then the blood-brain barrier restricts entry of therapeutic agents, but this prevents effective treatment of neurological disorders

Engineering Contradiction:
Improvedelivery effectiveness to CNSVSAvoidblood-brain barrier restriction
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses block copolymer nanoparticles as intermediary carriers to transport therapeutic polypeptides across the blood-brain barrier. The nanoparticles with core-shell morphology protect the polypeptide payload and facilitate its passage through the restrictive BBB, enabling effective CNS delivery without direct penetration by the therapeutic agent itself

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the physical and chemical parameters of the therapeutic delivery system by formulating polypeptides into nanoparticle complexes with controlled size, charge, and surface properties. These parameter changes enable the complexes to interact with BBB transport mechanisms and achieve effective brain delivery

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If exogenously administered substances are used, then peripheral factors limit presentation and crossing of BBB, but this reduces therapeutic availability

Engineering Contradiction:
Improvetherapeutic agent availabilityVSAvoidperipheral clearance and sequestration
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary protective action by encapsulating therapeutic polypeptides within block copolymer nanoparticles before administration. This pre-encapsulation protects the substances from peripheral enzymatic degradation, clearance, and sequestration, ensuring they remain available for BBB crossing and CNS delivery

Inventive Principle:
Principle #10Preliminary action

3Reliability

If nanoparticles are used for delivery, then site-specific and sustained delivery is achieved, but this increases device complexity

Engineering Contradiction:
Improvetargeted delivery to CNSVSAvoidnanoparticle formulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs segmentation by designing block copolymers with distinct functional segments: a hydrophobic core for polypeptide loading and a hydrophilic shell for stability and biocompatibility. This segmented architecture enables targeted CNS delivery while maintaining relatively simple formulation and synthesis procedures

Inventive Principle:
Principle #1Segmentation

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 polypeptide-polyion complexes effectively cross the BBB, delivering therapeutic agents to the CNS, providing neuroprotection and targeting neurological disorders by maintaining enzymatic activity and stability, while avoiding cytotoxicity and aggregation, thus overcoming the limitations of traditional drug delivery methods.

Implementation Method 1

the block copolymer self-assembles into nanoparticles

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

a synthetic polymer, wherein said synthetic polymer is a block copolymer comprising at least one water soluble, nonionic segment and at least one polyion segment

Methodology Applied
Scientific EffectAmphiphilic interaction: Amphiphiles

Implementation Method 3

said polyion segment comprises at least one charge opposite to the charge of the therapeutic polypeptide

Methodology Applied
Scientific EffectElectrostatic attraction: Ion Repulsion/Attraction

Data Source

PatentEP2152293B1Compositions for protein delivery and methods of use thereof
Publication Date: 2016.10.19 BOARD OF RGT UNIV OF NEBRASKA
  • EP2152293B1 patent drawingFigure 1A~1F
  • EP2152293B1 patent drawingFigure 1G
  • EP2152293B1 patent drawingFigure 2A~2B

AI summary

Compositions and methods for the delivery of a protein of interest are provided.