Poly(beta-amino ester) Coated Nanoparticles for MDR Overcoming

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Solution Overview

Problem

Current chemotherapy for cancer is impaired by the development of multidrug resistance (MDR) in cancer cells, which limits the efficacy of chemotherapeutic agents due to efflux mechanisms, and existing nanoparticle-based therapeutics face challenges in reproducible fabrication and controlled drug release.

Innovation Solution

Development of nanoparticles with a poly(beta-amino ester) coating that includes therapeutic agents and anchoring groups, allowing for efficient drug delivery and imaging capabilities, using a biodegradable and pH-sensitive poly(beta-amino ester) copolymer with a superparamagnetic iron oxide core for targeted drug delivery and imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If complex multi-step synthesis procedures are used for nanoparticle fabrication, then therapeutic agents can be loaded onto the nanoparticle, but batch-to-batch inconsistencies and variations in drug loading occur

Engineering Contradiction:

Improvedrug loadingVSAvoidbatch-to-batch consistency

Core Design Contradiction:

Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent combines multiple functional components (therapeutic agent, anchoring group, and polymer backbone) into a single integrated poly(beta-amino ester) copolymer structure. This merging of functions into one molecular entity eliminates the need for separate loading steps, thereby ensuring consistent drug loading across batches while maintaining effective therapeutic agent incorporation.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The therapeutic agent and anchoring group are pre-incorporated into the poly(beta-amino ester) copolymer during synthesis, before the nanoparticle formulation step. This preliminary integration ensures that every nanoparticle receives the same predetermined amount of drug, eliminating variability in drug loading across batches.

Inventive Principle:

Principle #10Preliminary action

2Reliability

If conventional chemotherapy is used, then treatment can be administered, but multidrug resistance develops limiting efficacy

Engineering Contradiction:

Improvechemotherapy efficacyVSAvoidmultidrug resistance

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The poly(beta-amino ester) copolymer acts as an intermediary carrier that delivers the therapeutic agent directly into cancer cells, bypassing the ABC transporter efflux mechanisms that cause multidrug resistance. The nanoparticle-mediated delivery system circumvents the resistance mechanism by utilizing endocytic pathways rather than passive diffusion that is blocked by MDR.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Adaptability or versatility

If theranostic nanoparticles are developed, then non-invasive monitoring is enabled, but fabrication complexity increases

Engineering Contradiction:

Improveimaging and therapy capabilityVSAvoidfabrication procedure

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent merges therapeutic and diagnostic functionalities into a single integrated nanoparticle platform. The poly(beta-amino ester) copolymer can be configured to carry both therapeutic agents and imaging agents, eliminating the need for separate fabrication processes for therapeutics and diagnostics, thereby reducing overall fabrication complexity while maintaining versatility.

Inventive Principle:

Principle #5Merging (Combining)

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 achieve enhanced intracellular drug accumulation and prolonged release, overcoming MDR and improving chemotherapy efficacy while providing non-invasive monitoring through magnetic resonance imaging.

Implementation Method 1

superparamagnetic iron oxide nanoparticles (SPIONs) are appealing owing to their intrinsic superparamagnetism that provides contrast in magnetic resonance imaging (MRI)

Methodology Applied

Scientific EffectSuperparamagnetism: Superparamagnetism

Implementation Method 2

poly(beta-amino ester) copolymer with a superparamagnetic iron oxide core for targeted drug delivery and imaging

Methodology Applied

Scientific EffectpH-sensitive protonation:

Data Source

PatentUS9687569B2Theranostic nanoparticle and methods for making and using the nanoparticle

Publication Date: 2017.06.27 UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION

AI summary

Nanoparticle having a poly(beta-amino ester) coating. The poly(beta-amino ester) coating includes one or more therapeutic agents that can be delivered by the particle and one or more anchoring groups that couple the polymer to the nanoparticle's core surface. In certain embodiments, the poly(beta-amino ester) includes one or more polyalkylene oxide groups. The poly(beta-amino ester) can further include a targeting agent to target the nanoparticle to a site of interest and a diagnostic agent that allows for imaging of the particle. Methods for making and using the nanoparticles are also provided.