Copolymères antibactériens synthétiques dégradables pour applications thérapeutiques (septembre 2021 – 2024)

State of art

The rise of antibiotic resistance is probably one of the main actual and future public health challenges. Even if antibiotics have saved and still save millions of lives every year, all of them have been accompanied by the development of bacterial resistance few years after their introduction on the market. One explanation of the drug-resistance phenomenon comes from the action mechanism of antibiotics, which is based on their interaction with ADN, ARN, or enzyme of the bacteria. After few contacts with antibiotics, bacteria are able to mutate or to inactivate the drugs and become drug-resistant or worse multi-drug resistant. « ESKAPE » pathogens exhibit a high level of antibiotic resistance and are today the main causes of nosocomial infections that lead to around 2 million of illness and 23,000 deaths. Face to this warning situation, researchers try to find new antibiotics but the majority of the recent molecules proposed on the market like the new generation of β-lactamines do not present a higher efficiency and are based on the same action mechanism. It is therefore highly urgent
to find alternatives to antibiotics.
Cationic synthetic amphiphilic antibacterial copolymers (sACs) appear as promising candidates with a high antibacterial activity associated with a low toxicity. Amphiphilic sACs contain cationic, hydrophobic, and hydrophilic groups and each of these components performs a specific function. Although the field of sACs is today highly dynamic (1,500 publications in 2020 with the keywords antibacterial polymer), their activity has been quite exclusively studied in vitro due to the non-degradability (C-C backbone) of the vast majority of the copolymers. In the last two years, few publications reported very encouraging results on synthetic degradable cationic antimicrobial copolymers (i.e. copolymers with cleavable functions in themain chain) for in vivo applications. Nevertheless,mainly all of these synthetic degradable cationic antimicrobial copolymers are based on the same polycarbonate backbone, limiting the structural parameter that could be modified. Thus, to have more room for innovation in a such very important field, the preparation of other kinds of degradable sACs whose structural parameters could be deeply investigated will be highly desirable for
developing/improving the use of sACs for in vivo application.

The copolymerization of hydrophobic, cationic and cyclicmonomers will allow to prepare such
new antibacterial compounds. The (bio)degradability will be also investigated. These
copolymers will be further be tested to find the more efficient antibacterial compounds with
the minimal cytotoxicity. The in vitro and ex vivo testing will be performed in Marseille (AMU,
iSM2 and AMU, UMR_MD1 ). Finally, the best candidates will be tested in vivo in collaboration
with the “Université de Nantes”.

References : Tardy, A., et al., Angew. Chem.-Int. Edit. 2017, 56, 16515; Tardy, A., et al., Chem. Rev. 2017, 117, 1319.

Work of the PhD student: Synthesis of the degradable antibacterial copolymers by radical
ring-opening polymerization. Characterization of the copolymers and in particular by SEC and
NMR. Study of the copolymers degradation by DLS, SEC or NMR.

Location: Institut de Chimie Radicalaire (UMR 7273, Aix-Marseille Université, Marseille,
France) in the CROPS team (Chimie Radicalaire Organique et Polymères de Spécialité)

Duration: 3 years
Funding: ANR
Position available: from September 2021
Candidature profile: Engineer or master 2 student with a good knowledge in polymer
synthesis and organic chemistry.

Contact: CV and motivation letter to send to Dr. Yohann Guillaneuf (yohann.guillaneuf@univ-
amu.fr) and Dr. Catherine Lefay (catherine.lefay@univ-amu.fr)