Degradation and in vivo evaluation of an innovative delayed release implant of medical grade poly(glycolide-co-trimethylene carbonate-co-ε-caprolactone)

Delayed release implants are a potential method to deliver a therapeutic after a specified lag time. A reservoir implant fabricated by dip-coating allows facile loading of a payload designed to be injected subcutaneously with release controlled by the physicochemical properties of a soft biodegradable terpolymer, poly(glycolide-co-tri- methylene carbonate-co-epsilon-caprolactone). A triphasic profile is achieved, consisting of a lag period (Phase 1) due to negligible terpolymer degradation preventing payload release. By 37 days (Phase 2) bulk erosion of the terpolymer reaches a state where payload begins to diffuse into the surrounding medium, accounting for 75 % of release and 20 % mass loss, indicating a combination of diffusion and erosion-mediated release. Lastly, Phase 3 is predominately diffusion-controlled as 20 % payload release is achieved with minimal mass loss of the polymer. In a rodent preclinical model, the terpolymer was well-integrated within host tissue with a balanced foreign body reaction. This study demonstrates the feasibility of using a unique medical grade poly(ester)-based polymer to develop a delayed release implant with excellent potential for translation. Prospective applications of this device include the delivery of sensitive payloads such as protein vaccines as polymer-payload interactions during manufacturing are avoided.