Toward Targeted Invasive Predator Control: Developing pH-Responsive Subcutaneous Implants for Native Mammals

Abstract

Introduced predators are a significant threat to global biodiversity and are responsible for most of all modern bird, reptile, and mammal extinctions. In Australia, the introduced feral cat (Felis catus) kills 459 million mammals annually and leaves many species facing extinction. Attempted reintroductions of threatened mammal species often fail due to the persistence of intractable feral cats�termed "problem individuals"�and the swift depredation of the reintroduced population. Biomaterial implants could hold the key to targeting problem individuals. Herein, we report the development of the population-protecting implant, a subcutaneous implant for native mammals. The implant is intended to be inert within the subcutaneous environment for the life of the native mammal and to release a toxic payload in the gastric environment of a feral cat when ingested during a predation event. By toxifying and causing the death of the feral cat, the problem individual is eliminated, and the remaining population of native mammals is protected from further predation. To achieve this, an innovative reverse enteric coating was developed for use as a biomaterial, which exhibited a previously unreported level of pH selectivity for solubility at gastric pH. Large batches of implants were manufactured via fluidized-bed spray coating with a uniform reverse enteric coating and low intrabatch variability. Implants with a 300 μm coating afforded significant stability and retention of the payload at subcutaneous pH in vitro, with rapid release of the payload observed at gastric pH. In addition, implants exhibited favorable stability in vivo in rats, with no observed difference in biocompatibility compared to conventional radio-frequency identification microchips. This work demonstrates a proof of concept of an innovative type of implant and serves as the basis for its future development and translation into the field.

Composition-Property Relationships of pH-Responsive Poly[(2-vinylpyridine)-co-(butyl methacrylate)] Copolymers for Reverse Enteric Coatings

“…Investigation of the effectiveness of the PVBI copolymer formulations, was not conducted due to their poor solubility at pH 2. However, the application of PVBI 50/30/20 is described elsewhere [ 42 ]. Generally, Suglets ® coated with the PVB or PVBM copolymer formulations did not exhibit any significant signs (qualitatively) of ineffective coating ( Supplementary Materials , Figure S8 ).…”

pH-Responsive Polymer Implants for the Protection of Native Mammals: Assessment of Material Properties and Poison Incorporation on Performance

“…Thus, there is a need to protect threatened mammal populations from problem individual predators, through the development of innovative and targeted control methods. One such method is the use of population protecting implants (PPIs) [ 19 , 20 ]. PPIs are subcutaneous implants with a pH-responsive coating and a poison core.…”

“…PPIs are subcutaneous implants with a pH-responsive coating and a poison core. These are small, poison implants designed for implantation into native mammals during reintroduction or monitoring programs, as a means of targeting problem individuals [ 20 ]. If a feral cat preys upon and consumes a ‘toxic Trojan’ [ 19 ] native mammal, it will also ingest the implant due to their specific feeding habits and the diminutive size of the implant [ 21 ].…”

“…Recently, we reported the prototypical development of the PPI [ 20 ], including the use of a pH-responsive, reverse enteric coating [ 22 ], and a non-toxic ‘core’, which will rapidly dissolve in the gastric environment of the feral cat (pH 1.6) [ 23 , 24 ]. The implants were manufactured via a batch-type fluidised-bed spray coating method.…”

“…The implants were manufactured via a batch-type fluidised-bed spray coating method. Beginning with a substrate that enabled spray coating—a small piece of cylindrical ABS filament—a core coating was applied that contained a non-toxic (sodium acetate, NaOAc) formulation [ 20 ]. This was followed by a pH-responsive copolymer coating, that was soluble at pH ≤ 1.5, but insoluble at pH ≥ 2.0 (i.e., a reverse enteric coating), due to the protonation (at low pH) of the basic 2-vinylpyridine moieties in the copolymer structure.…”