Encapsulation of Nanocrystals in Mannitol-Based Inhalable Microparticles via Spray-Drying: A Promising Strategy for Lung Delivery of Curcumin

Abstract

Background/objectives: Curcumin is well known for its great anti-inflammatory and antioxidant efficacy, representing a potential strategy for the treatment of respiratory disorders. However, several drawbacks, such as chemical instability, poor water solubility and rapid metabolism, result in low bioavailability, limiting its clinical applications. In this study, curcumin nanocrystals were incorporated into mannitol-based microparticles to obtain an inhalable dry powder.

Methods: A curcumin nanosuspension was produced by wet-ball media milling and thoroughly characterized. Spray drying was then used to produce mannitol microparticles incorporating curcumin nanocrystals. In vitro release/dissolution tests were carried out in simulated lung fluids, and the aerosolization properties were evaluated using a Next-Generation Impactor (NGI, Apparatus E Ph. Eu.).

Results: The incorporation of curcumin nanocrystals into mannitol-based microparticles influenced their morphological properties, such as geometric diameters, and flowability. Despite these changes, nebulization studies confirmed optimal MMAD values (<5 µm), while multi-step dissolution/release studies evidenced the influence of mannitol.

Conclusions: The developed curcumin nanocrystals-loaded mannitol microparticles show promise as an inhalable treatment for respiratory diseases, combining effective aerodynamic properties with controlled drug release.

Keywords: curcumin; inhalable microparticles; nano into micro; nanosuspension; pulmonary delivery.

Figure 1

(A) Composition and DLS data of the CUR-nanosuspension and (B) SEM micrographs of (a) curcumin raw powder and (b) CUR-nanosuspension.

Figure 2

SEM images of (A) the produced empty microparticle samples M10, M10_AB1 and M15, and (B) the produced curcumin-loaded microparticle samples C0.5_M10, C1_M10, C1_M10_AB1, C0.5_M15 and C1_M15. (magnification 3000×; the bar represents 20 µm).

Figure 3

Representative DSC thermograms of (A) raw curcumin, P188 and CUR-nanosuspension; (B) mannitol, C0.5_M10, C1_M10_AB1 and C1_M15 samples.

Figure 4

Release/dissolution profiles of pure CUR-nanosuspension and the CUR-NC loaded microparticles in simulated lung fluid (SLF) at 37 °C. (n = 3).

Figure 5

Deposition of (A) empty MP and (B) CUR-NP MP on the stages of the NGI after testing with Breezhaler^® at a flow rate of 90 l min⁻¹ (* p < 0.05) (MOC = micro-orifice collector).