A Novel Oral Astaxanthin Nanoemulsion from Haematococcus pluvialis Induces Apoptosis in Lung Metastatic Melanoma.

Hsing-Yu Haung,Hui-Min David Wang,Chaogeng Xiao,Wenyi Kang,Ying-Chen Cheng,Shang-Hsiu Hu,Yi-Chen Wang,Dengyong Liu,Daoud Ali

doi:10.1155/2020/2647670

Abstract

Astaxanthin (AST) is a naturally occurring xanthophyll carotenoid having the potential to be used as an anticancer agent; however, the human body has a low bioavailability of AST due to its poor solubility in the water phase. Therefore, we applied D-α-tocopheryl polyethylene glycol succinate (TPGS) as an emulsifier and natural edible peanut oil to form a steady oil-in-water (O/W) nanoemulsion loaded with AST (denoted as TAP-nanoemulsion). TAP-nanoemulsions were stable without the droplet coalescence against thermal treatments (30-90°C), pH value changes (over a range of 2.0-8.0), and ionic strength adjustments (at NaCl concentrations of 100-500 mM) measured by dynamic light scattering (DLS). AST within TAP-nanoemulsion was released up to 80% in a simulated intestinal enzymatic fluid in vitro, and the overall recovery rate was fairly consistent in the Caco-2 cellular model. In order to further evaluate in vivo melanoma inhibitory experiments, we injected the fluorescent-stained B16F10 cells into female C57BL/6 mouse tail veins and treated TAP-nanoemulsion in an oral gavage. qRT-PCR and Western blot demonstrated that TAP-nanoemulsion triggered effectively the apoptosis pathway, including enhancements of cleaved caspase-3 and caspase-9, ataxia-telangiectasia mutated kinase (ATM), and p21WAF1/CIP1 (p21) and decreases of B-cell lymphoma 2 (Bcl-2); cyclins D, D1, and E; mitogen-activated protein kinase (MEK); extracellular signal-regulated kinases (ERK); nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB); and matrix metallopeptidase-1 and metallopeptidase-9 (MMP-1 and MMP-9) in both gene and protein expressions. In conclusion, this study suggests that TAP-nanoemulsion with the oral treatment has a positive chemotherapy effect in melanoma with lung metastases in vivo. As far as we know, this is the first time to demonstrate that an antioxidant in nanoparticle administration cures lung metastatic melanoma.

Highlights

Haematococcus pluvialis is very famous for its excellent powerful antioxidative property and is one of the widespread freshwater Chlorophyta species from Haematococcaceae family members [1]
It is well known that oil and water are immiscible because of polar properties, and the interfacial tension between two phases is fairly high
We found that AST was slowly released from simulated intestinal surroundings, and the released amount was higher over 80% after another 6 hrs in the second digestive phase

Summary

Introduction

Haematococcus pluvialis is very famous for its excellent powerful antioxidative property and is one of the widespread freshwater Chlorophyta species from Haematococcaceae family members [1]. The high quantity of AST is produced in H. pluvialis resting cells, which are secreted and speedily accumulated while the ecological situations develop unfavorably for cell proliferation. This species yielded AST in low accessibility of nutrients, high salinity, and strong bright sunshine irradiation. AST might be limited in aquaculture, medicine, cosmetics, and functional food ingredient business applications due to its low stability in storage and poor solubility in the water phase for the human body. The benefit of nanoemulsion is having a higher surface area than the conventional emulsion and having better bioavailability and physicochemical stability due to the smaller droplet size [7]

Methods

Results

Conclusion