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

Projektinformationen

NanoPep4IBD

ID Finanzhilfevereinbarung: 101109065

DOI

10.3030/101109065

Projekt abgeschlossen

EK-Unterschriftsdatum 24 März 2023

Startdatum 1 September 2023

Enddatum 31 August 2025

Finanziert unter

• Marie Skłodowska-Curie Actions (MSCA)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 183 600,96

Koordiniert durch

UNIVERSITAT WIEN
Austria

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

Berichtszeitraum: 2023-09-01 bis 2025-08-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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.