Crosslinked Degradable Nanoparticles for Controlled Drug Release

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Solution Overview

Problem

Conventional biodegradable nanoparticles, particularly those based on poly(ε-caprolactone) and aliphatic polyesters, face issues with irreproducibility in size and shape, and lack of pendant functional groups, which complicates the modification of physicochemical, mechanical, and biological properties such as hydrophilicity and biodegradation rate.

Innovation Solution

Development of degradable polyester nanoparticles with crosslinked structures and functionalized polymers that allow for reproducible particle size and shape, and the incorporation of pendant functional groups to modulate properties, enabling effective encapsulation and delivery of pharmaceutical or biologically active agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If conventional biodegradable nanoparticles based on poly(ε-caprolactone) and aliphatic polyesters are used, then they provide basic drug delivery functionality, but they exhibit irreproducibility in size and shape and lack pendant functional groups for property modification

Engineering Contradiction:

Improveability to modify physicochemical and biological propertiesVSAvoidreproducibility of particle size and shape

Core Design Contradiction:

Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent introduces crosslinking degree as a controllable parameter to achieve reproducible nanoparticle formation. By systematically varying crosslinking conditions and polymer composition ratios, the invention establishes parameter ranges that yield consistent particle size and shape while enabling functional group incorporation for property modulation.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates composite nanoparticle systems combining degradable polyester matrices with crosslinking agents and functionalized polymers. This composite approach simultaneously achieves structural stability for size reproducibility and chemical functionality for property modification, resolving the contradiction between manufacturing precision and adaptability.

Inventive Principle:

Principle #40Composite materials

2Reliability

If crosslinked structures are introduced to improve nanoparticle stability and control drug release, then sustained release and reduced cytotoxicity are achieved, but particle size and shape control becomes more challenging

Engineering Contradiction:

Improvestability and sustained release performanceVSAvoidcontrol over particle size and shape

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent applies preliminary crosslinking to the polymer matrix before nanoparticle formation. By pre-establishing the crosslinked network structure in the bulk polymer, the invention eliminates crosslinking variability during nanoparticle synthesis, thereby achieving both stable nanoparticle morphology and reliable sustained release performance.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention separates the crosslinking function from the nanoparticle formation process by using pre-crosslinked polymer segments. This segmentation allows independent optimization of crosslinking density for stability and nanoparticle processing parameters for size control, resolving the contradiction between reliability and manufacturing precision.

Inventive Principle:

Principle #1Segmentation

3Adaptability or versatility

If pendant functional groups are incorporated to enable property modulation, then hydrophilicity and biodegradation rate can be tuned, but the complexity of polymer synthesis increases

Engineering Contradiction:

Improveability to tune hydrophilicity and biodegradation rateVSAvoidcomplexity of polymer synthesis

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent introduces functionalized crosslinking agents as intermediaries that provide pendant functional groups during the crosslinking process. This approach incorporates functional groups without requiring separate polymer synthesis steps, thereby achieving property modulation while minimizing synthesis complexity.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention merges the crosslinking function with the functional group incorporation function by using crosslinking agents that simultaneously provide both structural crosslinks and pendant functional groups. This combination eliminates separate synthesis steps and reduces overall process complexity while maintaining adaptability.

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS11254786B2Multifunctional degradable nanoparticles with control over size and functionalities

Publication Date: 2022.02.22 VANDERBILT UNIV

AI summary

In one aspect, the invention relates to polymers, crosslinked polymers, functionalized polymers, nanoparticles, and functionalized nanoparticles and methods of making and using same. In one aspect, the invention relates to degradable polymers and degradable nanoparticles. In one aspect, the invention relates to methods of preparing degradable nanoparticles and, more specifically, methods of controlling particle size during the preparation of degradable nanoparticles. In one aspect, the degradable nanoparticles are useful for complexing, delivering, and releasing payloads, including pharmaceutically active payloads. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.