The effect of formulation morphology on stimuli-triggered co-delivery of chemotherapeutic and MRI contrast agents

Most conventional chemotherapeutics have narrow therapeutic windows, and thus their delivery remains challenging and often raises safety and efficacy concerns. Theranostic platforms, with simultaneous encapsulation of therapeutic and diagnostic agents, have been proposed as next-generation formulations which can overcome this issue. In this work, we used electrohydrodynamic approaches to fabricate core@shell formulations comprising a pH responsive Eudragit L100 shell embedded with superparamagnetic iron oxide nanoparticles (SPIONs), and a thermo-responsive poly(N-isopropylacrylamide) (PNIPAM)/ethyl cellulose core loaded with the model drug carmofur. By varying the weight ratio of core polymer to shell polymer, the morphology of PNIPAM/ethyl cellulose@Eudragit L100 microparticles could be changed from concave to spherical. Smooth cylindrical fibres could also be generated. All the formulations exist as amorphous solid dispersions of drug-in-polymer, with distinct core@shell architectures. The fibres have clear thermo-responsive drug release profiles, while no thermoresponsive properties can be seen with the particles. All the formulations can protect SPIONs from degradation in gastric fluids (pH similar to 1.5), and around the physiological pH range the materials offer effective and pH-responsive relaxivity. The r(2) values also display clear linear relationships with drug release data, suggesting the potential of using MRI signals to track drug release in vivo. Mathematical equations were established to track drug release in vitro, with very similar experimental and predicted release profiles obtained.

Automated summary

In this study, core-shell formulations were prepared using electrohydrodynamic approaches for theranostic applications. By varying the weight ratio of core polymer to shell polymer, the morphology of the particles could be controlled. All formulations exhibited clear thermo-responsive drug release profiles and could protect diagnostic agents from degradation in gastric fluids.