Polymeric Implants for the Long-Acting Delivery of Biologics

3/22/2022 14:30 - 15:00

While decades-old drug products offering long-acting sustained delivery of small molecules and peptides exist, comparable systems that deliver biologics remain elusive. Protein drugs, such as monoclonal antibodies, are vitally important in the treatment of various diseases – including cancer, autoimmune disorders, asthma, and diseases of the eye – and a system capable of sustained delivery of a protein would be attractive in a number of indications.

But there are big problems that stand in the way of realizing a long-acting drug delivery system for biologics.

  • Stability: The function of a protein drug is usually tied to its tertiary structure, and this structure is inherently unstable. Protein stability is particularly challenging in the face of elevated temperatures, organic solvents, and acids – which are common in many long-acting drug delivery formulations.
  • Potency: Many important protein drugs are less potent than the small molecule drugs that have been successful in long-acting drug delivery systems. A viable long-acting implant will have to be highly loaded to carry a large payload of drug. Controlling the release rate when highly loaded with a drug is difficult with many conventional polymeric long-acting delivery systems.
  • Control of release rate: In highly loaded polymeric drug delivery systems, the release rate of the drug can be strongly dependent on the drug loading. Typically, when a polymeric system is loaded with a drug at approximately 60% or greater a hydrophilic protein rapidly releases. A successful drug delivery system for a protein will provide a mechanism to reduce release rate when highly loaded, and ideally offers a mechanism to tune release rate independent of loading.
  • Manufacturing: The ideal system for the drug delivery of a protein should take advantage of existing and established manufacturing methods.

We are developing a polymeric drug delivery implant for the long-acting delivery of a protein that addresses these four challenges. In our approach, protein is combined with ethylene-vinyl acetate (EVA) using conventional hot melt extrusion equipment, which eliminates the need for organic solvents. EVA is capable of very low processing temperatures in extrusion, can be highly loaded with a drug while maintaining usable mechanical properties, and will not produce acidic byproducts. To control the release rate of the drug, our implant consists of a drug-loaded core surrounded by a rate-limiting membrane that can be tuned to target relevant release rates. This multilayer structure is realized via coextrusion.

This contribution will present our system and example data derived from selected model proteins.

Christian Schneider, New Business Development Manager, Celanese Corp