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.

Injectable, thermoresponsive hydrogels are promising candidates for the delivery, maintenance and controlled release of adoptive cell therapies. Therefore, there is significant interest in the development of cytocompatible and biodegradable thermoresponsive hydrogels with appropriate gelling characteristics. Towards this end, a series of thermoresponsive copolymers consisting of poly(caprolactone) (PCL), poly(ethylene glycol) (PEG) and poly(propylene glycol) (PPG) segments, with various PEG:PPG ratios, were synthesised via ring-opening polymerisation (ROP) of ε-caprolactone and epoxy-functionalised PEG and PPG derivatives. The resultant PCL–PEG–PPG copolymers were characterised via proton nuclear magnetic resonance (1H NMR) spectroscopy, gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). The thermoresponsive characteristics of the aqueous copolymer solutions at various concentrations was investigated using the inversion method. Whilst all of the copolymers displayed thermoresponsive properties, the copolymer with a ratio of 1:2 PEG:PPG exhibited an appropriate sol–gel transition (28 °C) at a relatively low concentration (10 wt%), and remained a gel at 37 °C. Furthermore, the copolymers were shown to be enzymatically degradable in the presence of lipases and could be used for the encapsulation of CD4+ T-cell lymphocytes. These results demonstrate that the thermoresponsive PCL–PEG–PPG hydrogels may be suitable for use as an adoptive cell therapy (ACT) delivery vehicle.

Predation of threatened fauna by native and introduced predators can drive extinction and prevent population recovery. Most predator management involves exclusion or culling. Evidence suggests that exclusion may have detrimental effects on a prey species' predator awareness. At the same time, culling can cause selection of control‐resistant predators. There is increasing interest in harnessing evolutionary processes to drive adaptation of threatened fauna to cope, but there is limited attention on trying this from the predator direction. We need to shift the survival advantage away from predators that avoid lethal control, and go on to kill, towards those that demonstrate behaviors that reduce impact on threatened fauna. Instead of driving undesirable predator selection, could we select through management actions desirable traits to make them “less lethal” to threatened fauna? We draw on experimental research on predator aversion that suggests there may be an alternative way to mitigate the impacts of predators, while maintaining the learning opportunities of prey species. Using the case study of the invasive red fox in Australia, we propose a conceptual framework within which future research and management could occur to select for these desirable traits in predators and develop practical regimes for predator impact mitigation.

The use of pH-responsive polymeric micelles is a promising approach to afford the targeted, pH-mediated delivery of hydrophobic drugs within the low-pH tumour milieu and intracellular organelles of cancer cells. However, even for a common pH-responsive polymeric micelle system—e.g., those utilising poly(ethylene glycol)-b-poly(2-vinylpyridine) (PEG-b-PVP) diblock copolymers—there is a lack of available data describing the compatibility of hydrophobic drugs, as well as the relationships between copolymer microstructure and drug compatibility. Furthermore, synthesis of the constituent pH-responsive copolymers generally requires complex temperature control or degassing procedures that limit their accessibility. Herein we report the facile synthesis of a series of diblock copolymers via visible-light-mediated photocontrolled reversible addition-fragmentation chain-transfer polymerisation, with a constant PEG block length (90 repeat units (RUs)) and varying PVP block lengths (46–235 RUs). All copolymers exhibited narrow dispersity values (Đ ≤ 1.23) and formed polymeric micelles with low polydispersity index (PDI) values (typically <0.20) at physiological pH (7.4), within a suitable size range for passive tumour targeting (<130 nm). The encapsulation and release of three hydrophobic drugs (cyclin-dependent kinase inhibitor (CDKI)-73, gossypol, and doxorubicin) were investigated in vitro at pH 7.4–4.5 to simulate drug release within the tumour milieu and cancer cell endosome. Marked differences in drug encapsulation and release were observed when the PVP block length was increased from 86 to 235 RUs. With a PVP block length of 235 RUs, the micelles exhibited differing encapsulation and release properties for each drug. Minimal release was observed for doxorubicin (10%, pH 4.5) and CDKI-73 exhibited moderate release (77%, pH 4.5), whereas gossypol exhibited the best combination of encapsulation efficiency (83%) and release (91% pH 4.5) overall. These data demonstrate the drug selectivity of the PVP core, where both the block molecular weight and hydrophobicity of the core (and accordingly the hydrophobicity of the drug) have a significant effect on drug encapsulation and release. These systems remain a promising means of achieving targeted, pH-responsive drug delivery—albeit for select, compatible hydrophobic drugs—which warrants their further investigation to develop and evaluate clinically relevant micelle systems.

Background Drug-eluting gastrointestinal (GI) stents are emerging as promising platforms for the treatment of GI cancers and provide the combined advantages of mechanical support to prevent lumen occlusion and as a reservoir for localized drug delivery to tumors. Therefore, in this work we present a detailed quality assurance study of 5-fluorouracil (5FU) drug-eluting stents (DESs) as potential candidates for the treatment of obstructive GI cancers. Methods The 5FU DESs were fabricated via a simple two-step sequential dip-coating process of commercial GI self-expanding nitinol stents with a 5FU-loaded polyurethane basecoat and a drug-free protective poly(ethylene-co-vinyl acetate) topcoat. The drug loading, content uniformity and drug stability were determined using a validated high-performance liquid chromatography (HPLC) method, which is also recommended in the United States Pharmacopeia. In vitro drug release studies were performed in phosphate buffered saline to determine the drug releasing properties of the two 5FU-loaded stents. Gas chromatography (GC) and HPLC were employed to determine total residual tetrahydrofuran and N,N -dimethylformamide in the stents remaining from the manufacturing process. Sterilization of the stents was performed using gamma radiation and stability testing was carried out for 3 months. Results The drug loading analysis revealed excellent uniformity in the distribution of 5FU between and within individual stents. Determination of drug stability in the biorelevant release media confirmed that 5FU remains stable over 100 d. In vitro drug release studies from the stents revealed sustained release of 5FU across two different time scales (161 and 30 d), and mathematical modeling of drug release profiles revealed a diffusion-controlled mechanism for the sustained 5FU release. GC and HPLC analysis revealed that the daily residual solvent leached from the stents was below the United States (US) Food and Drug Administration (FDA) guidelines, and therefore, unlikely to cause localized/systemic toxicities. Sterilization of the stents with gamma radiation and accelerated stability tests over a period of 3 months revealed no significant effect on the stability or in vitro release of 5FU. Conclusion Our results demonstrate that the 5FU DESs meet relevant quality standards and display favourable drug release characteristics for the potential treatment of GI cancers and related obstructions.