Theses (MSc. Molecular Medicine)

Zerumbone (ZER) is an 11-membered crystalline sesquiterpene from the rhizome of Zingiber zerumbet, which carries many beneficial properties, including anti-inflammatory and antioxidant properties. In chronic obstructive pulmonary disease (COPD), zerumbone targets several inflammatory and oxidative mediators released by broncho-epithelial cells and alveolar macrophages in various pathways resulting in the suppression of the disease progression. However, zerumbone has many several drawbacks such as low bioavailability, poor gastrointestinal (GI) absorption and non-specific targeting of tissues and organs, all of which limits the development of ZER as potential new drug formulation for the treatment of COPD. Liquid crystalline nanoparticles (LCN) are novel drug delivery carrier that have tuneable characteristics to enhance and ease the delivery of bioactive compounds. Loading ZER into LCNs can potentially overcome the drawbacks of free ZER on its own. In this study, ZERLCNs were investigated for their ability to inhibit cigarette smoke extract induced inflammation, oxidative stress and senescence (the main characteristics of COPD) through in vitro study in human healthy bronchoepithelial cell line (BCiNS1.1) and mice macrophage (RAW264.7). The study compared the biological activity of ZER-LCNs with pure ZER powder. The results from this study indicated that ZER-LCNs had advantageous physicochemical parameters including a sustained in vitro release as well as a high entrapment efficiency. Additionally, the in vitro cellular studies showed that the ZER-LCNs had potent anti-inflammatory and antioxidant properties in both the BCi-NS1.1 and RAW 264.7 by regulating the genes and cytokines produced during inflammation and oxidative stress. The broncho-epithelial cells treated with ZER-LCNs inhibited the senescence induced by cigarette smoke extract by regulating the gene and protein expression of p21 and p16 (a marker of senescence). The research found that ZER-LCNs have superior biological activity compared to free ZER against cigarette smoke extract induced oxidative stress, inflammation, and senescence. This suggests the unique tuneable characteristics of ZER-LCNs and promising potential development for widescale pharmaceutical use. Additional in-depth studies involving animal model or clinical study on the mechanistic effect of ZER-LCN for its anti-inflammatory, antioxidative and antisenescence properties is required to validate its potential to treat COPD. Keywords: Zerumbone, liquid crystalline nanoparticles, monoolein, P407, anti-inflammatory, antioxidant, entrapment efficiency, drug release.