Paradigm-changing, versatile, scalable and cost-effective technology for monthly injections of peptide drugs

PROJECT SUMMARY/ABSTRACT Delivery of peptide drugs via non-invasive routes results in poor bioavailability and short plasma half-lives, hence most are delivered by injections or implants. While conjugation/modification and microencapsulation of peptide drugs in polymers have been highly successful, the success of peptide modification is limited by weekly injections, the need for new active pharmaceutical ingredients (APIs) for each peptide, and inconsistent blood levels causing side effects. By contrast, microencapsulation of peptides in polymers (i.e., poly(lactic-co-glycolic acid, PLGA) has advantages of much longer intervals between injections (>weeks to months) and use of existing APIs, thus reducing regulatory obstacles. However, current microsphere encapsulation strategies suffer from lack of terminal sterilization, poor yields, problematic scale-up, residual organic solvent levels that limit storage stability of the final products and non-zero-order release. New and improved delivery strategies are critically needed to accelerate development and utilization of peptide drugs. Here, we propose to develop a cost-effective, extremely simple, efficient, and generalizable water-based PLGA microsphere encapsulation technology for peptides. This proposal will focus on formulation and optimization of sterile remote-loading microspheres for constant delivery of commercial peptide drugs. These formulations will be tested for their pharmacokinetics after single monthly injections vs. monthly commercial depots or daily injections of free peptide.