pH-responsive subcutaneous implants prepared via hot-melt extrusion and fluidised-bed spray coating for targeted invasive predator control

Globally, invasive mammalian predators are responsible for the depredation and extinction of threatened species. The development of innovative control methods that target the most impactful of these predators is crucial to ensure the successful conservation of threatened species. Feral cats (Felis catus) are one of the most damaging invasive mammalian predators, particularly in Australia, where they are estimated to kill more than 1.5 billion mammals, birds, and reptiles annually. Mammals are disproportionally depredated by feral cats, and efforts to reintroduce or conserve remnant populations of threatened mammal species are hampered by shortfalls in current control methods. To address this challenge, we have prototyped the population-protecting implant (PPI), a subcutaneous implant that is designed to target the most dangerous and efficient predators, so called 'problem individuals'. Conceptually, the implant has a reverse enteric coating that is stable in the subcutaneous envi-ronment of a prey animal but dissolves rapidly in the gastric environment of a predator, resulting in the release of a toxic payload and death of the predator. In this work we report a novel approach for the manufacture of PPIs, that combines hot-melt extrusion and fluidised-bed spray coating, to respectively afford implants with accurate drug loading and a uniform reverse-enteric coating. Most of the implants bearing a 300 mu m coating were found to effectively contain their payload for more than 280 d in vitro, in a simulated subcutaneous environment (pH 7.4, 37 degrees C) but release it within 2.5 h in vitro under simulated gastric conditions (pH 1.5, 37 degrees C). However, two failures were observed at 64 d and 200 d, likely due to the increased osmotic pressure caused by the soluble core. This work highlights a revised implant design that may improve implant stability in vivo and facilitate the translation of the PPI to field use, for the conservation of threatened species. We also introduce a novel and facile approach to determine the loading of non-chromophoric payloads in hot-melt extruded systems that is highly relevant for the determination of active pharmaceutical ingredients in drug-delivery formulations.