PLGA Microspheres for Controlled Nitric Oxide Release

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Solution Overview

Problem

Current nitric oxide (NO) donors face challenges due to low stability in biological environments and potential side effects, limiting their effectiveness and safety for prolonged use in biomedical applications.

Innovation Solution

Development of biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating S-nitroso-N-acetylpenicillamine (SNAP) that release nitric oxide in a controlled and sustained manner, with tunable release rates and stability enhanced by copper ions or light exposure, minimizing toxic by-products and adverse effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If gaseous NO is administered topically or inhaled for therapeutic treatments, then therapeutic effects are achieved, but administration becomes cumbersome and lifetime is short

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidadministration convenience

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent uses PLGA microspheres as an intermediary carrier to deliver NO donors to the target site. The microspheres encapsulate NO donor molecules (such as NONOates or S-nitrosothiols), protecting them from premature degradation and enabling controlled release at the wound site, thus improving administration convenience while maintaining therapeutic effectiveness

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The NO donor molecules are pre-encapsulated within PLGA microspheres before administration. This preliminary encapsulation stabilizes the unstable NO donors, protects them from degradation in biological environments, and prepares them for controlled release at the target site, extending their effective lifetime and simplifying administration

Inventive Principle:

Principle #10Preliminary action

2Reliability

If NO donors are administered to achieve therapeutic effects, then antimicrobial and vasodilating effects are obtained, but stability is low especially in biological environments

Engineering Contradiction:

Improvetherapeutic effectVSAvoidchemical stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

PLGA microspheres serve as a protective intermediary that shields unstable NO donor molecules from degradation in biological environments. The biodegradable polymer matrix provides a controlled release environment that maintains donor stability while enabling gradual NO release for sustained therapeutic effects

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the physical and chemical parameters of NO delivery by encapsulating donors within PLGA microspheres. This changes the release kinetics from rapid degradation to controlled diffusion, extending the effective lifetime of NO donors in biological environments while maintaining therapeutic stability

Inventive Principle:

Principle #35Parameter changes

3Reliability

If NO donors are used to achieve therapeutic benefits, then growth factor stimulating and smooth muscle relaxant effects are obtained, but potential side effects and toxic by-products occur

Engineering Contradiction:

Improvetherapeutic benefitVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The PLGA microsphere carrier acts as a controlled delivery intermediary that releases NO donors gradually at the target site. This controlled release minimizes systemic exposure and reduces the formation of toxic by-products, thereby maintaining therapeutic benefits while reducing side effects

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent achieves localized delivery of NO donors through PLGA microspheres at the wound site. This local release ensures high concentration of NO where needed for therapeutic effects while minimizing exposure of other tissues to potential side effects and toxic by-products

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 PLGA-SNAP microspheres provide prolonged, controlled release of nitric oxide for therapeutic applications, enhancing stability and safety, suitable for wound healing and other biomedical uses by maintaining physiologically relevant NO levels for extended periods without adverse effects.

Implementation Method 1

biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating S-nitroso-N-acetylpenicillamine (SNAP) that release nitric oxide

Methodology Applied

Scientific EffectBiodegradation: Decomposition (biological)

Implementation Method 2

stability enhanced by copper ions or light exposure

Methodology Applied

Scientific EffectCopper ion catalysis: Catalysis

Implementation Method 3

stability enhanced by copper ions or light exposure

Methodology Applied

Scientific EffectPhotolysis: Photodissociation

Data Source

PatentUS11439609B2Nitric oxide releasing PLGA microspheres for biomedical applications

Publication Date: 2022.09.13 THE RGT UNIV OF MICHIGAN

AI summary

A polymeric composition includes poly(lactide-co-glycolide) (PLGA) microspheres; and at least one of a discrete RSNO adduct or a polymeric RSNO encapsulated within the microspheres, with the at least one of the discrete RSNO adduct or the polymeric RSNO adduct capable of releasing nitric oxide (NO). The polymeric composition exhibits stability under dry conditions at 37° C. and prolonged and controllable NO release rates, when exposed to light capable of photolyzing an RSNO bond, or when exposed to moisture, for a predetermined amount of time from the at least one of the discrete RSNO adduct or the polymeric RSNO adduct.