Dry powder aerosols of curcumin-chitosan nanoparticle complex prepared by spray freeze drying and their antimicrobial efficacy against common respiratory bacterial pathogens

• Spray freeze drying produced highly aerosolizable curcumin nanoplex aerosols.
• Aerosol transformation diminished supersaturation generation of curcumin nanoplex.
• Curcumin was released more slowly from aerosols than from aqueous suspension.
• Curcumin nanoplex aerosols maintained activity against respiratory pathogens.
• Curcumin nanoplex aerosols exhibited minimal cytotoxicity towards lung cells.

While the therapeutic benefits of curcumin delivery to the lung to treat various pulmonary disorders have been established, development of inhaled curcumin formulation that can address its inherently low aqueous solubility remains lacking. Although curcumin nanocapsules prepared by conventional encapsulation methods can improve the dissolution rate, their intricate preparation makes them less attractive for widespread implementation. Recently, our group developed a new class of curcumin nanoparticles in the form of curcumin-chitosan nanoparticle complex (or curcumin nanoplex in short) by a simple, cost-effective, and highly efficient method based on self-assembly drug-polysaccharide complexation. Owing to its nanosize and amorphous state, the curcumin nanoplex possessed high supersaturation generation capability upon dissolution that in turn produced high apparent solubility of curcumin.In the present work, we developed dry powder aerosol formulation of the curcumin nanoplex by spray freeze drying (SFD) using l-leucine and d-mannitol as adjuvants. The curcumin nanoplex aerosols were found to exhibit excellent aerosolization efficiency attributed to their large and low-density morphology, and the presence of l-leucine – a well-established aerosol dispersion enhancer – in their matrix. The aerosols, however, exhibited weaker supersaturation generation capability compared to the aqueous nanoplex suspension due to their slower dissolution rates caused by irreversible aggregations of the nanoplex during SFD. Nevertheless, the curcumin nanoplex aerosols still produced apparent solubility that was approximately 50% higher than the native curcumin’s solubility, thus signifying their dissolution enhancement capability. Despite their slower dissolution rate, the curcumin nanoplex aerosols maintained the same antimicrobial activity as the nanoplex suspension against four clinically-derived respiratory bacterial pathogens (i.e. Pseudomonas aeruginosa, Burkholderia cepacia, Klebsiella pneumoniae, and Stenotrophomonas maltophilia). Lastly, the aerosols exhibited minimal cytotoxicity towards the lung epithelium cells just like the native curcumin.

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