Inhaled non-steroidal polyphenolic alternatives for anti-inflammatory combination therapy

• Main Authors: Lee, Sie Huey, Heng, Desmond, Xavier, Vanessa Joanne, Chan, Kok Ping, Ng, Wai Kiong, Zhao, Yanli, Chan, Hak-Kim, Tan, Reginald B. H.
• Other Authors: School of Materials Science & Engineering
• Format: Article
• Language: English
• Published: 2020
• Subjects: Science::Chemistry; Dry Powder Inhaler; Polyphenol
• Online Access: https://hdl.handle.net/10356/138015
• Institution: Nanyang Technological University

The inhaled corticosteroids are considered the first line of defence for the treatment of persistent asthma and COPD in adults and children. However, clinically, up to 50% of asthmatics and the majority of COPD patients have been reported to respond sub-optimally to inhaled corticosteroid therapy. Therefore, reduced responsiveness to corticosteroids or in extreme cases, a complete lack of response even to high doses, is becoming a growing cause of concern to the medical community. This work therefore seeks to circumvent the problem via pioneering an inhalable non-steroidal polyphenolic dry powder combination comprising curcumin, quercetin and trans-resveratrol from the phenolic acid, flavonoid and stilbene classes respectively, for benign anti-inflammatory therapy (without the corticosteroid-linked side effects). The optimized L-leucine-containing spray-dried powder was partially crystalline and moisture-resistant, and the powder particles were of respirable-size (d50 of ~1.95 ± 0.03 μm), corrugated and porous. When dispersed via an Aerolizer® inhaler at 60 l/min, the powder showed concomitant in-vitro deposition with robust FPFs of ~44%. Significant improvements to the drug release rate and extent were also achieved. Favorably, the optimized formulation was comparable to the mainstream corticosteroids, budesonide and beclomethasone dipropionate, and more potent than an ivy leaves extract preparation, in inhibiting GM-CSF release from inflamed A549 cells. Potentially, this corticosteroid-sparing inhaled alternative might be a potent yet safer treatment option for juvenile, corticosteroid-resistant, or even mainstream patients.