Bando a Cascata 2024 del Research Node 3 - Sistemi di Drug Delivery Intelligente per la Gestione delle Infezioni Resistenti agli Antibiotici

Chronic wounds are the hard-to-heal wounds that arise for a variety of reasons, including responding to an underlying disease that represents a challenge for global public health. Treatment for different types of wounds comprise dressing or topical agents with a variety of purposes, including maintenance of a moist healing environment; reduction of bacteria infecting wound; and prevention of infection. The most common causative organisms associated with wound infections include many MDR species such as methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, vancomycin-resistant Enterococci (VRE), Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter spp. (CRAsp). The medical need for novel antimicrobial MDR treatment options globally is undeniable. However, modern drug discovery and development is a lengthy and arduous process, that most often culminate in high failure rates due to safety and toxicity issues, among many other issues. Thus, the research community is willing to invest in various drug discovery strategies, one of which is drug repurposing or repositioning aimed to find new uses for existing drugs, often combined.

One of the limitations of traditional combined therapies lie in their inability to guarantee the simultaneous delivery of various drugs in all districts and to bacterial cells, above all if related to a dense inoculum. Recent studies identified the heart of the problem lies in the intricacies of combined therapy. In particular, the absence of chemical interactions between different drug molecules means that, when administered together, these molecules reach individual bacteria separately.

The smart drug release systems as hydrogels, nanocarriers, patches and microneedles together with multi-target drugs can contribute to solve some of the medical needs of patients suffering from chronic wounds.Significant advances have also been made in the development of functionalized nanomaterials which can acts as stimuli-responsive systems allow the delivery of antibiotics directly to the site of infection, The use of appropriate delivery systems can ensure effective doses because they can reach intracellular targets (S. aureus), increasing bioavailability at the site of action and bacterial exposure. Moreover, some delivery systems can increase permeability across the bacterial cell wall, especially in case of gram-negatives. Thus, improved delivery and synergistic combinations between existing antibiotic and other antimicrobial substances can interfere with such mechanisms that can promote antibiotic-resistance tendency like quorum-sensing mechanisms, biofilm formation, efflux pumps functionality and the host immune response, ultimately overcoming resistance.

Projects responding to this call should aim to develop smart antimicrobial delivery systems as patches, microneedles (MNs) loaded with hydrogel or multidrug systems for the management of antibiotic resistant articular or skin infections able to promote interferences with many mechanisms of antibiotic-resistance tendency like quorum-sensing mechanisms, biofilm formation, efflux pumps functionality and the host immune response, ultimately overcoming resistance.

Expected Results:

• Smart drug release systems can give significant advances, improving the efficacy and safety of antimicrobial drugs, offering many advantages over other conventional delivery systems such as non-invasiveness, controlled-release pattern, avoidance of first-pass metabolism. Moreover, these systems can enhance the pharmacokinetics and biodistribution of antimicrobial drugs, increasing their effective bioavailability, reducing their dosage frequency, and improving their antimicrobial efficacy against biofilm-related infections, while slowing down the development of antimicrobial resistance.

• Calls will be open to teams including both private and public entities located in Sourthern Italy(minimum: 3, maximum: 5 entities), external to the INF-ACT consortium and to members of the beneficiary team of the COC-1-2023-UNICT call.
• Each team must identify a lead organization (Leader), or the subject appointed and authorized to represent the whole team and maintain communications with the Spoke during all phases of the presentation and evaluation procedure and for the entire duration of the activities planning;
• The team Leader must be a public University or a public Research Organization;
• Each team Leader may submit only one project proposal in response to this call. On the other hand, the possibility is not precluded for the same entity to be part of other teams in response to other Cascade Calls
• Each team entity must indicate the name of the researchers involved in the proposed project activities (so-called "critical mass"), the expected commitment in person-months, their curriculum vitae to assess the actual contribution to the research work.
• Each team entity must participate with at least one researcher. The maximum number of researchers to be involved as critical mass for this project is 12.
• 100% of the requested financing must be dedicated to entities located in regions of Southern Italy (tagging: territorial);
• In case of recruitment of new researchers, the team must comply with the provisions of article 47 "Equal opportunities, generational and gender, in public contracts PNRR and PNC" of Law Decree 31-May-2021, no. 77 converted into law 29-July-2021, n. 108;
• Budget breakdown and financial reporting must comply with guidelines and regulation for RRNP funded-projects.

The call text (in Italian) was published on the UNICT website - A correction has also been published.

Collection of applications started at 12:00 PM on Apr 19, 2024 and closed at 12:00 PM on May 22, 2024
Evaluations are currently in progress

• All allocated funds must be spent by the end of October 2025. Should MUR allow time extensions to the NRRP/PNRR INF-ACT project, extensions might be also provided to COC projects;
• Awarded teams will comply to NRRP/PNRR reporting rules as per the indications that will be made by INF-ACT Spoke and INF-ACT Foundation;
• Awarded teams will have to join the INF-ACT foundation as partners;
• Funding should be acknowledged in all publications emanating from the research carried out during the award period together with NRRP/PNRR funds using the following statements: "This research was supported by EU funding within the NextGenerationEU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT). [BENEFICIARY NAME] was recipient of INF-ACT Cascade Open Call 2024 (ID CALL)."
• Participation of private entity and co-financing are not mandatory, but an added value;
• Financial capacity of private entity will be assessed ex-post by third parties. In case of negative outcome, the private entity will be excluded from participating to the awarded project and, therefore, from receiving funding.

Proposals are being evaluated on the basis of the following evaluation criteria:

• Objective and scientific quality (max 50 points)
• Innovation and private sector involvement (max 20 points)
• Impact (max 15 points)
• Economic sustainability (max 15 points)

Proposals will be considered admissible for financing if they obtain at least 70 out of 100 points. Evaluation will be carried out by a panel of 3-5 international and highly-qualified scientists, who are not directly involved in the INF-ACT Research Program. Reviewers will sign a declaration to exclude possible conflicts of interest before accessing the scientific proposals to be evaluated.