Review on Medusa^®:a polymer-based sustained release technology for protein and peptide drugs

Abstract

The polymer-based Medusa^® system (Flamel Technologies) has been designed for slow release of therapeutic proteins and peptides. The Medusa II consists of a poly l-glutamate backbone grafted with hydrophobic α-tocopherol molecules, creating a colloidal suspension of nanoparticles (10 – 50 nm) in water. The sustained drug release is based on reversible drug interactions with hydrophobic nanodomains within the nanoparticles. In vivo, it is suggested that the therapeutic protein is displaced by endogenous proteins present in physiological fluids, leading to a slow drug release. The peak concentration is dramatically decreased and the protein release substantially extended. The Medusa technology has been applied to subcutaneous injection for several therapeutic proteins, such as IL-2 and IFN-α_2b, in animal models (rats, dogs, monkeys) and clinical trials in renal cancer (IL-2) and hepatitis C (IFN-α_2b) patients.

Keywords::

• animal models
• clinical trials
• polymer–protein complexes
• slow release

Acknowledgements

We are grateful to C Trepo, Hopital l'Hotel-Dieu, Lyon, France for his contribution to the IFN-α trials. WH Fridman, Georges Pompidou Hospital, Paris, France and N Thiounn, Necker Hospital, Paris, France, are acknowledged for their participation in the IL-2 trial. In addition, the contributions of S Angot, M Bordeaux, O Breyne, D Chognot, A Constancis, C Grangeon, H Hardre, G Pouliquen, C Thomas and C Vialas at Flamel Technologies are acknowledged. We are also thankful to R Jorda (Flamel Technologies) for his critical assessment of the manuscript.

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