Medusa® Platform Description
Medusa hydrogel (pGluVE, or PGA A1) is based on a hydrophilic biodegradable polyglutamate chain grafted with hydrophobic Vitamin E. The polymer self assembles in aqueous medium to form a stable solution of nano-sized hydrogels comprising multiple polymer chains and 95% water. The hydrogel is formed by hydrophobic interactions only, no chemical cross linking agent is required.
After subcutaneous injection, a depot is formed at the injection site and the fully active biologic is slowly released in vivo over one to fourteen days in humans.
Based on hydrophobic and/or electrostatic interactions, this association step is performed conveniently in water at room temperature, without the use of any organic solvents, heat or shear mixing. The liquid formulation containing the hydrogel can be sterile filtered, then filled in vials or cartridges or freeze-dried and reconstituted in water. The scale-up and transfer of the formulation process are easy and do not require sophisticated handling or reactors.
Vaccine Applications
DeliVax™, Medusa’s vaccine applications, permits the efficient formulation of vaccines.
Medusa Platform Performance
- Improves safety profile compared to immediate release formulations, i.e. lower Cmax and more regular concentration (AUC) of the biologics delivered;
- Permits the extended delivery of drugs from 1 day up to 14 days without loss of activity of the biologic, improving therapeutic benefit;
- May be used to solve threshold issues:
- Allows the controlled-release of poorly soluble as well as highly soluble biologics;
- Applicable to unstable molecules; and
- May be used to prevent aggregation or refolding/reconditioning of peptides and proteins
- Applicable to low dose or high dose biologics.
Medusa Platform Advantages
Industry-endorsed platform with ongoing partnerships with Merck Serono, Pfizer and several other undisclosed leading pharmaceutical and biotechnology companies.
- Medusa polymer is safe: non-immunogenic and non-toxic, with no local irritation nor allergic reactions, as proven in numerous human clinical trials;
- Versatile “Bio friendly” injectable formulation compatible with a wide range of variables:
- size;
- structure,
- physico-chemical properties (hydrophobicity, hydrophilicity, charges contents) and stability (e.g. cytokines, blood factors, hormones, metabolic peptides or proteins , antibodies and fragments thereof, and vaccines).
- Subcutaneous administration and potential for other routes of administration (intra-muscular, intravenous, ocular, intra-joint, intra-thecal, etc.);
- Maintains the full activity of biologics (no protein engineering and/or chemical modifications required, with consequent lack of additional impaired immunogenicity);
- Preserves the structural integrity of peptide/protein antigens for vaccine applications (DeliVax™).
- Non-denaturing formulation and delivery of fully structured and active biologics;
- Fully biocompatible and biodegradable nanogels: glutamic acid and Vitamin E are Generally Recognized As Safe (GRAS);
- Cost effective, easy to implement and scale-up process using mostly water (solvent- and surfactant-free); and
- Strong intellectual property position and Freedom to Operate (no third party licensing obligations).
Medusa’s Key Advantages Over Standard Long-acting Formulation Platforms for Biologics
Publication
Medusa: an Innovative Formulation Approach to Improve Pharmacokinetic & Safety Profiles of Biotherapeutics
Chan Y.-P., Meyrueix R., Rivail C. and Chatellier J. (2011) ONdrugDELIVERY “Injectable Drug Delivery 2011: Formulation Focus”
Issue August 2011: 4-6.
Review on Medusa®: a polymer-based sustained release technology for protein and peptide drugs
Chan Y-P., Meyrueix R., Kravtzoff R., Nicolas F. and Lundstrom K. (2007) Expert Opinion on Drug Delivery 4: 441-451.
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 a-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.
