Design of polymeric core-shell carriers for combination therapies.

Particle engineering for co-delivery of drugs has the potential to combine multiple drugs with different pharmaceutical mechanisms within the same carrier, increasing the therapeutic efficiency while improving patient compliance. This work proposes a novel approach for producing polymer-polymer core-shell microparticles by multi-step processing of emulsion and spray drying. The particle core was obtained by an oil-in-water emulsion of poly(ε-caprolactone) (PCL) loaded with curcumin (CM), followed by the resuspension in poly(vinyl alcohol) (PVA) containing ciprofloxacin (CPx) forming the shell layer by spray-drying. The obtained core-shell particles showed an average size of 3.8 ± 1.2 µm, which is a suitable size for inhalation therapies. The spatial distribution of the drugs was studied using synchrotron-based macro attenuated total reflection Fourier transform infrared (macro ATR-FTIR) microspectroscopy to map the chemical distribution of the components within the particles and supported the presence of CM and CPx in the core and shell layers, respectively. The formation of the core-shell structure was further supported by the differences in the release profile of CM from these particles, when compared to the release profile observed for the single particle structure (PCL-CM). Both empty and drug-loaded carriers (up to 100 µg.mL-1) showed no cytotoxic effects on A549 cells while exhibiting the antibacterial activity of CPx against Gram-positive and Gram-negative bacteria. These polymer core-shell microparticles provide a promising route for the combination and sequential drug release therapies, with the potential to be used in inhalation therapies.