Therapeutic peptide self-assembly and formulations – ArchiPex

The Labcom project “ArchiPex” is based on the dual complementarity industry/basic research and galenic /physical chemistry. This project is born of a 15 year fruitful collaboration between Franck Artzner (IPR, UMR6152 , Rennes) and his colleague Maité Paternostre and IPSEN laboratory teams. During this period we focused on the study and understanding of the physical chemistry of lanreotide and triptorelin assemblies. The work performed in this context resulted in i) the placing on the market of a drug, ii) 3 patents and iii) 12 publications, including 5 in high impacts factor journals (2 PNAS, 2 JACS and 1 Nature Materials).

The original idea on which this laboratory is based is that a drug can perform its own formulation by spontaneously forming a gel. This “self-formulation” principle has been validated on Somatuline Autogel ® marketed now in over 50 countries. The great interest of this formulation is the slow release of the drug as it circulates in the blood over a month after the injection. In previous collaborations, Franck Artzner's and Maité Paternostre's teams have developed a number of tools and acquired a unique knowledge of peptide assembly and mechanism and the Ipsen laboratory an essential expertise of peptide self-formulations.

The Labcom ArchiPex will focus on the most promising molecule Lanreotide (also called Somatuline) with the following industrial objectives:
• PROTECTION from generics Somatuline Autogel® on the market since ten years by proposing new slow release formulations.
• INNOVATION by offering new release formulations of Lanreotide and designing new active molecules with self-assembly properties.

This innovation and development will be done through the deepening of our knowledge of the molecular mechanisms of peptide supramolecular self-assembly and especially Lanreotide) to understand and control the molecular interactions taking place in the assemblies, to identify the chemical groups and the physico- chemical parameters influencing the process. One of the major issues in the formulation of Somatuline is to reduce the viscosity of the gel to facilitate the injection using needles of smaller diameter and to increase the dose of peptide in the formulations. To do this, we will study the assembly formed by the Lanreotide in the presence of small molecules known to modify the physicochemical characteristics of water as co-solvents, by modulating the pH and the nature of the counterions. In parallel, Lanreotide analogues containing targeted modifications that do not affect its biological activity will be studied in the same way. The viscosity of Lanreotide and analogues gels obtained in these different conditions will be determined and the most promising in terms of viscosity will be tested in vitro to determine their rate of release. In a further selection we will choose the formulations to be tested on animals for their released properties. The teams will share their own experiences: the team in Rennes with the help of Maité Paternostre on the characterizations of Lanreotide gels and the team in Ipsen on the in vitro and in vivo release assays. This work will lead to new slow release formulations of Lanreotide and their developments that will be protected and published. The creation of an IPSEN/CNRS mixed laboratory (UMR) will be undertaken after the success of the ANR LabCom phase.