Electrospun Nanofiber Mesh for Controlled Phage Delivery

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Solution Overview

Problem

Current methods for delivering particulate materials, such as bacteriophages, to cells are inefficient and face challenges with bacterial resistance, particularly in treating topical bacterial infections, where traditional antibiotics are ineffective due to resistance and may have side effects.

Innovation Solution

The development of an electrospun nanofiber mesh treatment delivery system using iron-doped apatite nanoparticles (IDANPs) for controlled release of phages, combining a superficial rapid release layer of polyethylene oxide fibers doped with IDANPs and deeper coaxial polycaprolactone/polyethylene glycol blended polymer fibers for slow phage delivery, enhancing phage infection and killing of bacteria while minimizing harm to eukaryotic cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional antibiotics are used to treat bacterial infections, then bacterial growth can be inhibited, but bacterial resistance develops rapidly rendering the treatment ineffective

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidbacterial resistance

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses iron-doped apatite nanoparticles (IDANPs) as intermediary adjuvant particles that modify the bacterial surface to enhance phage attachment and infection efficiency. These nanoparticles serve as a mediator between the phage therapy and bacterial target, improving treatment effectiveness while avoiding antibiotic resistance mechanisms

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention combines phage particles with iron-doped apatite nanoparticles to create a composite therapeutic system. This composite approach leverages the biocompatibility and surface-modifying properties of the nanoparticles alongside the specific infectivity of phages, achieving enhanced antibacterial activity without promoting resistance

Inventive Principle:

Principle #40Composite materials

2Adaptability or versatility

If phage therapy is used to treat bacterial infections, then bacterial resistance develops more slowly, but delivery efficiency to target cells remains insufficient

Engineering Contradiction:

Improveresistance developmentVSAvoiddelivery efficiency

Core Design Contradiction:

Adaptability or versatilityVSProductivity

Solution Approach 1:

IDANPs act as intermediary carriers that facilitate phage delivery to bacterial cells. The nanoparticles attach to bacterial surfaces and serve as platforms for phage accumulation, significantly enhancing delivery efficiency while maintaining the slow resistance development characteristic of phage therapy

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies physical parameters of phage delivery by using nanoparticles to concentrate phages at the bacterial surface. This parameter change in delivery concentration and localization dramatically improves infection efficiency without altering the biological properties of the phage that confer slow resistance development

Inventive Principle:

Principle #35Parameter changes

3Reliability

If high concentrations of phage are delivered to maximize bacterial killing, then treatment effectiveness increases, but potential harm to eukaryotic cells may increase

Engineering Contradiction:

Improvebacterial killing efficiencyVSAvoideukaryotic cell toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by concentrating phage particles specifically at the bacterial cell surface through nanoparticle mediation. This localized delivery ensures high bacterial killing efficiency at the target site while minimizing phage exposure to and potential harm to surrounding eukaryotic cells

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

IDANPs serve as localized intermediaries that bind preferentially to bacterial surfaces, creating a concentrated delivery zone for phages. This intermediary approach enables high local phage concentrations for effective bacterial killing while the nanoparticle-bacterial specificity prevents widespread exposure to eukaryotic cells

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS11191721B1Particle delivery via small-scale morphology materials for antibacterial applications

Publication Date: 2021.12.07 GREGORY JESSICA M

AI summary

Disclosed herein is a particle delivery system comprising electrospun nanofiber comprised of coaxial fiber with a microfluidic core. Iron-doped apatite nanoparticles (IDANPs) have demonstrated a unique influence over phage killing of bacteria, whereby, IDANP-exposed bacterial cultures experience 2× the bacterial death as controls. IDANPs consist of hydroxyapatite (HA) doped with iron. HA is a mineral known to be biocompatible and analogous to the inorganic constituent of mammalian bone and teeth and has been approved by the Food and Drug Administration (FDA) for many applications in medicine and dentistry. Previous work has shown that for IDANPs to enhance antibacterial activity of phage to the greatest extent, bacterial cultures should be exposed to IDANPs for 1 hr prior to phage introduction. Biocompatible polymer materials which encase IDANPs and/or phage can be used to disseminate IDANPs and/or phage in a controlled manner into a physiological system for treatment of bacterial infection. When components of said materials contain micro- or nano-scale components, high surface-to-volume ratio for treatment delivery is garnered.