Abstract
To effectively achieve the pulmonary delivery for curcumin (CN), novel inhalable mucus-penetrating nanocrystal-based microparticles (INMP) were designed. The D-Tocopherol acid polyethylene glycol 1000 succinate (TPGS) modified CN nanocrystals (CN-NS@TPGS) were prepared by high pressure homogenization and further converted into nanocrystal-based microparticles (CN-INMP@TPGS) using spray-drying. It was demonstrated that CN-NS@TPGS exhibited little interaction with the negatively charged mucin due to a strong electrostatic repulsion effect and PEG hydrophilic chain, and exhibited a much higher penetration ability across the mucus layer compared with poloxamer 407 modified CN-NS (CN-NS@P407) and tween 80 modified CN-NS (CN-NS@TW80). The aerodynamic results demonstrated that the CN-INMP with 10% TPGS acting as the stabilizer presented a high FPF value, indicating excellent deposition in the lung after inhalation administration. Additionally, in vivo bioavailability studies indicated that the AUC(0-t) of CN-INMP@TPGS (2413.18 ± 432.41 µg/L h) were 1.497- and 3.32-fold larger compared with those of CN-INMP@TW80 (1612.35 ± 261.35 µg/L h) and CN-INMP@P407 (3.103 ± 196.81 µg/L h), respectively. These results indicated that the CN-INMP@TPGS were absorbed rapidly after pulmonary administration and resulted in increased systemic absorption. Therefore, the inhalable CN-INMP could significantly improve the bioavailability of CN after inhalation administration. The developed mucus-penetrating nanocrystals-in-microparticles might be regarded as a promising formulation strategy for the pulmonary administration of poorly soluble drugs.
Highlights
Pulmonary inhalation administration is an ideal way to locally treat lung diseases, such as chronic obstructive pulmonary disease, bronchitis and lung cancer [1–3], and to achieve systemic absorption for other diseases owing to the great surface area (70–140 m2 in the adult human lung) of the lung and fast transport of active ingredients across the respiratory epithelium [4–6].pulmonary formulations were restricted by the physiological barrier of the lungs, such as the complex branching structure, mucociliary clearance and macrophages phagocytosis [7], as well as the particles size and solubility of the drugs [8]
The results showed that the volume mean particle sizes(D50) of the freshly prepared CN-NS@Tocopherol acid polyethylene glycol succinate (TPGS), CN-NS@poloxamer 407 (P407), CN-NS@tween 80 (TW80) were 119.1 ± 2.12 nm, 121.87 ± 1.31 nm, and 131.08 ± 5.78 nm, respectively
It could be concluded that the CN-NS@TPGS exhibited a relatively lower negative charge potential compared with CN-NS@P407 and CN-NS@TW80
Summary
Pulmonary formulations were restricted by the physiological barrier of the lungs, such as the complex branching structure, mucociliary clearance and macrophages phagocytosis [7], as well as the particles size and solubility of the drugs [8]. The aerodynamic requirements could prove to be a great challenge for effective lung deposition for inhalation formulation. Owing to its suitable aerodynamic characterization, the INMP exhibits more effective lung deposition in comparison with conventional nanoparticles, and can Pharmaceutics 2022, 14, 538. Pharmaceutics 2022, 14, 538 nanoparticles, and can be reconstituted into drug nanocrystals when contacting mucus on the respiratory surface after deposition [13,14]. The particles size and surface properties of nanocrystals can significantly influence their fate (absorption or clearance) be reconstituted when contacting mucusundissolved on the respiratory surface in the lung. The particles size and surface properties of nanocrystals can significantly influence their fate (absorption or clearance) be reconstituted when contacting mucusundissolved on the respiratory surface in the lung. into
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
