Table 2.

Formulation development strategies and delivery systems of zerumbone.

Nr	Formulation Strategy	Method of Preparation	Components of Delivery System	Therapeutic Indication	Purpose	Major Results/Conclusions
1	Nanostructured lipid carriers [36]	Hot, high-pressure homogenization	Lipid dispersion: hydrogenated palm oil, olive oil, and lipoid S100 Aqueous dispersion: Sorbitol, Tween-80 and thiomersal	Leukemia	Treatment of leukemia	The zerumbone-loaded nanocarriers depict sustained release characteristics and high cytotoxicity in human T-cell acute lymphocytic leukemia.
2	Nanostructured lipid carriers [37]	Hot, high-pressure homogenization	hydrogenated palm oil, distilled water, olive oil, lipoid- S 100, lecithin, thimerosal, and sorbitol	Antileukemic effect and acute toxicity	Acute toxicity of zerumbone and zerumbone-loaded nanocarriers via the oral route of administration	Both zerumbone and zerumbone-loaded lipid nanocarriers at acute doses do not induce behavioral alterations, toxicological signs, or adverse effects.
3	Nanostructured lipid nanocarriers [35]	Hot, high-pressure homogenization	Lipid dispersion: hydrogenated palm oil, olive oil, and lipoid S100 Aqueous dispersion: Sorbitol, Tween-80 and thiomersal	Colorectal adenocarcinoma	Increase the potency and efficacy of zerumbone-loaded lipid nanocarriers	Zerumbone lipid nanocarriers depict slow release of the drug without altering the anti-cancer effect.
4	Nanostructured lipid nanocarriers [28]	Hot, high-pressure homogenization	Lipid dispersion: hydrogenated palm oil, olive oil, and lipoid S100 Aqueous dispersion: Sorbitol, Tween-80 and thiomersal	Canine mammary gland tumor	Antiproliferative effect and the mode of cell death on canine mammary gland tumor adenocarcinoma	Effective in inhibiting the proliferation and inducing apoptosis on the canine mammary gland tumor cells. Inhibition of Bcl-2 and activation of pro-apoptotic Bax gene expressions and activation of caspases of the intrinsic and extrinsic apoptosis pathways were reasons for the effect.
5	Inclusion complexes [60]	Inclusion complex through freeze-drying	Hydroxypropyl-β-cyclodextrin	Anticancer drug effect	Enhancement of solubility of zerumbone	Important modifications in the solubility and stability of zerumbone
6	Nanosuspensions [48]	High-pressure homogenization	Hydroxypropyl methylcellulose (HPMC) and sodium dodecyl sulfate (SDS)	Not applicable	Improve solubility and dissolution characteristic’s	Enhanced dissolution and saturation solubility of zerumbone.
7	Nanostructured lipid carrier gel [47]	Hot, high-pressure homogenization	Carbopol 980 used to prepare the nanostructured lipid carrier gel	Wound healing	Anti-inflammatory activity	The gel decreased inflammatory cell infiltration and degeneration and increased granulation in healing wound tissues. There was an increase of anti-inflammatory IL-10, decreased the pro-inflammatory TNF-α, IL-6 concentrations, and downregulated cyclooxygenase-2 gene expression.