Polypeptide hybrid nanoparticles for the delivery of inhalable drugs

Project Information

NANOINHALE

Grant agreement ID: 101103989

DOI

10.3030/101103989

Project closed

EC signature date 10 March 2023

Start date 3 April 2023

End date 2 April 2025

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 199 694,40

Coordinated by

ROYAL COLLEGE OF SURGEONS IN IRELAND
Ireland

Periodic Reporting for period 1 - NANOINHALE (Polypeptide hybrid nanoparticles for the delivery of inhalable drugs)

Reporting period: 2023-04-03 to 2025-04-02

Summary of the context and overall objectives of the project

Delivering medicines directly to the site of infection can make treatments more effective and reduce side effects. One promising way to achieve this is by using nanoparticles, tiny carriers that can transport drugs deep into the lungs or into wounds when combined with gels. For respiratory infections such as tuberculosis, inhalable nanoparticles could deliver drugs directly to the lungs where they are needed most. Similarly, for burn wounds, nanoparticles embedded in gels can steadily release healing drugs at the site of injury. However, developing such drug carriers is challenging. The particles must be stable, release drugs at the right rate, and break down safely in the body. They must also overcome biological barriers such as mucus, biofilms, and tissue structures that often block medicines from reaching their targets.
This project focused on creating new polypeptide-based nanoparticles made entirely from natural building blocks of amino acids and sugars. These materials are biocompatible, biodegradable, and easy to modify, allowing drugs to be attached or released in controlled ways. The nanoparticles are designed to penetrate mucus and target infected cells, making them especially suitable for use in nebulisers or in gel-based wound treatments. In the long term, this research aims to develop a versatile platform technology that could be adapted for treating a wide range of infectious diseases more effectively and safely.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

This project explored how polypeptide nanoparticles can be designed to deliver medicines more effectively. It was first studied how the type of amino acids used affects the size of the resulting nanoparticles, which is a key factor in how they behave in the body. It was found that nanoparticles made from amino acids that form helical structures tend to be smaller, while those that form more open, sheet-like structures are larger. By grouping amino acids according to their chemical properties, a predictive model was developed that provided a way to predict nanoparticle size directly from their amino acid composition. After evaluating the nanoparticles, they were used in a gel-based system for treating burn wounds rather than for inhalation. In this approach, the nanoparticles are embedded in an alginate hydrogel, which can respond to changes in pH or the acidicidy of the wound environment. Burn wounds typically start off more basic (around pH 8.5) and become more acidic (around pH 5) as they heal. The system was designed so that as the wound heals, the gel gradually softens and degrades, while the nanoparticles release their drug, Indomethacin, in response to pH changes. This means the treatment can adjust automatically during the healing process, reducing the need for repeated medical intervention. The combination of a biodegradable gel and smart, pH-responsive nanoparticles offers a promising way to deliver medicine precisely where and when it’s needed, helping wounds to heal more effectively and comfortably.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

This project set out to develop smart nanoparticles made from amino acids to deliver multiple drugs precisely where they are needed in the body. Initially, the goal was to test these nanoparticles for inhalation therapy using a nebuliser. A major scientific breakthrough was achieved in understanding how the chemical nature of amino acids determines the size of the nanoparticles produced. By analysing and modelling data from many formulations, a predictive model was created that links amino acid properties, such as molecular weight and structural tendencies, to the resulting particle size. This represents a significant advance over current approaches, which rely largely on trial and error to obtain particles of the desired size. The model provides valuable new design rules for researchers developing next-generation drug delivery systems. When challenges arose with the nebuliser technology, the project pivoted towards a new application: a nano-in-gel system for treating burn wounds. In this approach, the drug-loaded nanoparticles were embedded in a hydrogel that responds to changes in skin pH. Burned skin is more basic than healthy skin, and this difference triggers the controlled release of the anti-inflammatory drug Indomethacin from the nanoparticles. This innovative, self-regulating system could enable minimally invasive treatment of burn wounds, reducing pain and medical interventions while promoting healing. Although further testing is needed, the results demonstrate a novel and adaptable technology platform that advances the stet-of-the-art of nanoparticle-based drug delivery.