Novel gut-stable peptides and drug-delivery systems - possible treatment for IBD

Project Information

NanoPep4IBD

Grant agreement ID: 101109065

DOI

10.3030/101109065

Project closed

EC signature date 24 March 2023

Start date 1 September 2023

End date 31 August 2025

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 183 600,96

Coordinated by

UNIVERSITAT WIEN
Austria

Periodic Reporting for period 1 - NanoPep4IBD (Novel gut-stable peptides and drug-delivery systems - possible treatment for IBD)

Reporting period: 2023-09-01 to 2025-08-31

Summary of the context and overall objectives of the project

The project addressed the need for new treatments for inflammatory bowel disease (IBD) and gastrointestinal infections, two major global health problems with limited therapeutic options. Current treatments are often ineffective, cause significant side effects, or rely on antibiotics that contribute to the development of antimicrobial resistance. Many promising peptide-based and small-molecule drugs cannot be developed into oral medicines due to poor stability and/or solubility in the gastrointestinal tract. These challenges represent a significant barrier to the development of more effective and patient-friendly therapies.
The overall aim of this project was to develop gut-stable peptides effective against biofilms, peptides suitable for wound-healing treatment, and to design innovative nanoparticle-based delivery systems that allow their safe and targeted administration. Three main objectives guided the work: (1) to design and synthesise stable antimicrobial and wound-healing peptides, (2) to develop mesoporous silica nanoparticle systems for oral delivery and sustained release, and (3) to evaluate the antimicrobial and antibiofilm functions of developed compounds and the in vitro release profile of the formulations.
Beyond these research goals, the project contributed to the advancement of future peptide therapeutics and nanoformulations. Additionally, it offered extensive interdisciplinary training in peptide chemistry, nanotechnology, and drug formulation.

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

The project successfully combined peptide chemistry, recombinant expression, and nanotechnology to create new therapeutic candidates for intestinal diseases and infections.
Cathelicidin-based antimicrobial peptides and their analogues were designed and synthesised. Modified versions containing D-amino acids, retroinverso sequence designs, and β-amino acid residues were produced to improve structural stability. Comprehensive characterisation using NMR, LC-MS, circular dichroism, and molecular dynamics simulations confirmed that the new analogues retained a helical structure and had enhanced stability in gastrointestinal conditions.
Functional assays confirmed the antimicrobial and antibiofilm activity of the synthesised peptides, especially the all-D and retroinverso analogues.
In parallel, the project established a complete recombinant expression and folding protocol for the human TFF2 peptide, a small but hydrophobic wound-healing protein that had previously been difficult to produce. This achievement opens new possibilities for the study and therapeutic use of the trefoil factor family.
The second major result was the development of a mesoporous silica nanoparticle drug-delivery system. These nanoparticles achieved a more than 100-fold increase in solubility for the investigated compound, enabling pH-responsive, gut-targeted release and demonstrating their suitability for the oral delivery of poorly soluble drugs and peptides.

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)

The project achieved several results beyond the current state of the art. A recombinant expression system for the TFF2 peptide was successfully developed with improved yields, enabling future functional and therapeutic studies on this previously unaccessible peptide. Stable analogues of the antimicrobial peptide CATH-2 were produced, demonstrating enhanced stability and effective antimicrobial and antibiofilm activity, addressing the common degradation and solubility limitations of native peptides.
In parallel, the development of a mesoporous silica nanoparticle formulation platform enabled efficient enhancement of solubility and targeted gastrointestinal release. This platform has strong potential for controlled delivery of other bioactive molecules and for improving the oral bioavailability of peptide therapeutics.
The results have significant commercial and clinical potential. A patent draft has been prepared on the MSN nanoformulation platform, and industrial partners have been contacted for co-development. To ensure further uptake, proof-of-concept and follow-up funding applications have been submitted.
Future work will focus on scaling up nanoparticle production, validating peptide activity in animal models, and ensuring compliance with regulatory and safety requirements for translational use. Support from the Technology Transfer Office of the University of Vienna, together with ongoing collaborations and international networking, will facilitate commercialisation, licensing, and clinical translation. Overall, the project provides new therapeutic and formulation strategies that can transform peptide drug development and have a lasting impact on European biomedical innovation.