Multilayer matrix of nanofibres delivers probiotics to the right place in the gut

Breaking new ground 25. nov 2021 3 min Head of Section, Professor Anja Boisen Written by Kristian Sjøgren

By making a sandwich of nanofibres, researchers can deliver living bacteria from the mouth through the acidic stomach to the gut, which they can colonise and promote health.

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Having bacteria in our gut is beneficial.

Healthy gut bacteria are associated with good physical and mental health. Conversely, research has shown that inappropriate composition of gut bacteria may lead to the development of diseases such as diabetes, obesity and Alzheimer’s.

The pharmaceutical industry is therefore focusing intensely on how to deliver healthy bacteria (probiotics) into people’s intestines, with all the associated health benefits.

The challenge is that many probiotic bacteria do not survive the transit through the acidic stomach.

New research from the Technical University of Denmark is addressing this problem. Researchers have designed a multilayer sandwich of nanofibres to facilitate the enhanced delivery of probiotics from the mouth through all the barriers in the digestive tract to the intestine, where they can exert their beneficial effects.

“Our research focuses on developing technologies to deliver probiotics to the right place in the gut. They need assistance to get there, and the nanofibres can help to ensure this,” explains a researcher behind the new study, Anja Boisen, Professor and Head of Section, Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics, Department of Health Technology, Technical University of Denmark, Kongens Lyngby.

Fatemeh Ajalloueian, Associate Professor in the same department as Anja Boisen, is the first author of the article, published in Food Hydrocolloids. The research was carried out in collaboration with Tine R. Licht, Professor, National Food Institute, Technical University of Denmark.

Encapsulating bacteria in a matrix of nanofibres

Many beneficial gut bacteria are quite fragile and cannot survive stomach acid, and many of the bacteria being developed as new promising probiotics therefore have difficulty surviving even in a pill bottle or perish on the journey before reaching the intestines.

Anja Boisen and Fatemeh Ajalloueian have sought to overcome this delivery challenge by using nanofibres.

In their proof-of-concept study, the researchers designed an electrospun construct using an electric force to mould charged threads of polymer solution into nanofibres.

They used pullulan, an edible water-based polysaccharide, to safely encapsulate Lactobacillus rhamnosus GG bacteria, which are very healthy to have in your gut. The long strands of electrospun nanofibres were woven together in a matrix.

“We wanted to determine whether this is a good way to encapsulate bacteria. Lactobacillus rhamnosus GG survives well in pullulan, but their viability declined strongly when the monolayer matrix dissolved on contact with stomach acid,” says Anja Boisen.

Multilayer construct delivers bacteria intact to the gut

The researchers then tried to protect the nanofibre matrix with a sandwich of two electrospun layers of poly(lactic-co-glycolic acid) (PLGA). Like pullulan, PLGA does not harm people but is water-repellent.

The researchers made a multilayer construct with the bacteria encapsulated into pullulan nanofibres, with two electrospun PLGA layers covering it.

They fed this to rats and then examined their faeces and intestines to determine whether the bacteria encapsulated in the nanofibre matrix passed through the rats’ digestive system to the intestine.

The multilayer matrix of pullulan and PLGA protected the bacteria well during the transit from mouth to intestine.

The researchers found the bacteria in the rats’ faeces, and autopsies showed that the bacteria had colonised their intestines. According to Anja Boisen, further research will show whether the bacteria thereby colonise the gut at the factor of 10 the researchers hope for.

“The delivery method increased colonisation in the intestines. In this study, we tested the technology with bacteria that are not that fragile, but our upcoming study will use live microorganisms that are harder to deliver from the mouth to the intestine in adequate amounts,” explains Anja Boisen.

Bacteria in microcontainers with space for antibiotics

The researchers are also taking the technology a step further in an attempt to design an optimal method for inducing healthy bacteria to colonise our intestines to protect our health.

Anja Boisen says that the researchers are working on a new design. Instead of placing the nanofibres in a matrix, they are designing microcontainers that contain and protect the bacteria with a nanofibre coating and release them at the right time and in the right location in the gut.

These microcontainers also have more compartments than those containing the bacteria, so they can deliver other substances into the intestines.

The microcontainers are intended to pass from the mouth to the intestine, where they first release a small amount of antibiotics locally, killing the pre-existing bacteria.

Then the second compartment in the microcontainer opens, enabling the beneficial bacteria to colonise without competition.

“We are experimenting with different structures and solutions to deliver probiotics effectively into the intestine. Based on our initial experiment, some of the solutions we are considering look extremely promising,” concludes Anja Boisen.

Multi-layer PLGA-pullulan-PLGA electrospun nanofibers for probiotic delivery” has been published in Food Hydrocolloids. In 2017, the Novo Nordisk Foundation awarded a grant to Anja Boisen for the project MIMIO – Microstructures, Microbiota and Oral Delivery.

Anja Boisen is working on micro- and nano sensor development and microdevices for drug delivery. The sensor projects are focusing on micro- and nanose...

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