Ozonated Sunflower Oil Embedded within Spray-Dried Chitosan Microspheres Cross-Linked with Azelaic Acid as a Multicomponent Solid Form for Broad-Spectrum and Long-Lasting Antimicrobial Activity.

Multicomponent solid forms for the combined delivery of antimicrobials can improve formulation performance, especially for poorly soluble drugs, by enabling the modified release of the active ingredients to better meet therapeutic needs. Chitosan microspheres incorporating ozonated sunflower oil were prepared by a spray-drying method and using azelaic acid as a biocompatible cross-linker to improve the long time frame. Two methods were used to incorporate ozonated oil into microspheres during the atomization process: one based on the use of a surfactant to emulsify the oil and another using mesoporous silica as an oil absorbent. The encapsulation efficiency of the ozonated oil was evaluated by measuring the peroxide value in the microspheres, which showed an efficiency of 75.5-82.1%. The morphological aspects; particle size distribution; zeta potential; swelling; degradation time; and thermal, crystallographic and spectroscopic properties of the microspheres were analyzed. Azelaic acid release and peroxide formation over time were followed in in vitro analyses, which showed that ozonated oil embedded within chitosan microspheres cross-linked with azelaic acid is a valid system to obtain a sustained release of antimicrobials. In vitro tests showed that the microspheres exhibit synergistic antimicrobial activity against