Targeted Nano-formulations for Treatment of MRSA: A multicomponent platform for nano-formulated treatment of resistant microbial infections

Introduction

Many bacteria that cause infectious diseases develop resistance to not only the primary antibiotic treatments available in the clinic but also to drugs of last resort. These drugs often require long treatment periods and come with significant side effects.

Challenges in Drug Development

At the same time, many promising lead compounds with high activity and wide therapeutic windows have failed to progress to clinical trials due to:

1. Poor solubility
2. Protein absorption issues
3. Other difficulties in formulation (e.g., low drugability)

Proposed Solution

LeadtoTreat proposes a new solution to these challenges by introducing a platform for future infection treatment. This platform enables targeted delivery of novel lead compounds with low drugability, as well as synergistic combinations of antibiotics and potentiators in a nano-formulation.

Dual Targeting Approach

A novel dual targeting approach will be employed, which includes:

• Direct targeting toward the pathogenic bacteria
• Targeting areas of inflammation

This platform technology will be demonstrated by converting a highly active, but insoluble and protein-binding, novel compound into targeted nano-formulations for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections, with proven in vivo and in vitro safety.

Identification of Synergistic Combinations

Furthermore, LeadtoTreat aims to identify novel synergistic combinations of antibiotics and potentiators and convert these into highly active targeted nano-formulations for the treatment of MRSA infections.

Impact and Innovation

LeadToTreat will have a significant impact on the future treatment of microbial infections by:

• Demonstrating a pathway to co-delivery of synergistic combinations of existing antibiotics
• Revitalizing the huge library of abandoned low-drugability lead compounds

From an innovation perspective, it is expected to develop broadly applicable targeting tools for MRSA and a roadmap for other indications.

Project Management

The project will be managed by SINTEF (Norway), involving:

• Narodowy Instytut Lekow (National Medicine Institute, NMI, Poland)
• NanoTag Biotechnologies GmbH (NTB, Germany)