Multimeric ELP Fusions for Targeted Cyclosporine A Delivery

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Solution Overview

Problem

Existing synthetic nanoparticles for drug delivery suffer from dose-limiting toxicity, insufficient residence time in the body, and lack of targeted delivery to intended tissues.

Innovation Solution

Development of multimeric elastin-like polypeptides (ELPs) fused with drug binding domains, such as cyclophilin A or FKBP, to form drug carriers that self-assemble and target specific receptors, allowing controlled drug release and enhanced tissue specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If synthetic nanoparticles (dextran, PLGA, liposomes) are used for drug delivery, then drug encapsulation is achieved, but dose-limiting toxicity occurs

Engineering Contradiction:

Improvedrug delivery reliabilityVSAvoidtoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the material composition parameter from synthetic polymers (PLGA, dextran) to elastin-like polypeptides (ELPs) with specific amino acid sequences. This parameter change transforms the material properties to reduce toxicity while maintaining drug delivery functionality, as ELPs are biocompatible and biodegradable proteins that can be engineered with controlled phase transition temperatures for targeted drug release.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite structures by fusing ELPs with drug binding domains (such as cyclophilin A or FKBP). This composite approach combines the biocompatibility of ELPs with the specific drug binding capabilities of the fused domains, achieving both reduced toxicity and improved targeting efficiency simultaneously.

Inventive Principle:

Principle #40Composite materials

2Reliability

If synthetic nanoparticles are used for drug delivery, then drug encapsulation is achieved, but residence time in the body is insufficient

Engineering Contradiction:

Improvedrug delivery reliabilityVSAvoidresidence time

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent modifies the physicochemical parameters of the delivery system by using ELPs with tunable phase transition temperatures. By adjusting the amino acid composition and molecular weight of ELPs, the patent optimizes circulation time and residence time in the body, allowing the nanoparticles to remain in circulation long enough to reach target tissues while avoiding rapid clearance by the reticuloendothelial system.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If conventional nanoparticles are used, then drug delivery is achieved, but targeted delivery to intended tissues is lacking

Engineering Contradiction:

Improvedrug delivery reliabilityVSAvoidtargeted delivery capability

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent merges the ELP structural framework with specific drug binding domains (cyclophilin A, FKBP) to create multifunctional nanoparticles. This merging provides both the biocompatible carrier structure and the specific targeting capability in a single integrated molecule, enabling active targeting to tissues expressing specific receptors for the fused domains.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent introduces local quality by fusing specific binding domains to particular regions of the ELP structure. This allows different parts of the nanoparticle to have different functions: the ELP portion provides circulation and stability, while the fused drug binding domains provide localized targeting to specific tissues, creating spatially differentiated functionality.

Inventive Principle:

Principle #3Local quality

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 ELP fusions provide improved drug delivery by reducing toxicity, increasing residence time, and enhancing targeted delivery to tissues, effectively treating conditions like Sjögren's syndrome, autoimmune disorders, and cancer.

Implementation Method 1

ELPs have a unique inverse transition behavior. Below their transition temperature (Tt), they are highly water soluble but once the temperature rises above their Tt, ELPs undergo a phase separation process and self-assemble into different kinds of coacervates including different size particles

Methodology Applied

Scientific EffectPhase separation: Phase Change