Stabilized Astaxanthin Nanoparticles Developed Using Flash Nanoprecipitation to Improve Oral Bioavailability and Hepatoprotective Effects

Author:

Ghosh Antara1ORCID,Banik Sujan1ORCID,Yamada Kohei1ORCID,Misaka Shingen2ORCID,Prud’homme Robert K.3,Sato Hideyuki1ORCID,Onoue Satomi1ORCID

Affiliation:

1. Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan

2. Department of Bioregulation and Pharmacological Medicine, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan

3. Department of Chemical and Biological Engineering, A301 EQUAD, Princeton University, Princeton, NJ 80544, USA

Abstract

In this study, we developed stabilized astaxanthin (AX) nanoparticles (sNP/AX) to improve the physicochemical properties, oral bioavailability, and hepatoprotection of AX. A flash nanoprecipitation technique was used with a multi-inlet vortex mixer to prepare the sNP/AX. Vitamins E (VE) and C (VC) were used as co-stabilizers with poloxamer 407 as a stabilizer to inhibit the oxidative degradation of AX during sNP/AX formation and storage. VC stabilized AX in the aqueous phase during the preparation, whereas VE markedly improved the storage stability of sNP/AX, as evidenced by the AX contents remaining at 94 and 81% after 12 weeks of storage at 4 °C and 25 °C, respectively. The mean sNP/AX diameter was 215 nm, which resulted in higher AX release properties than those of crystalline AX. Rats, orally administered sNP/AX (33.2 mg AX/kg), exhibited higher systemic exposure to AX, whereas oral absorption in the crystalline AX group was negligible. In the rat hepatic injury model, oral pretreatment with sNP/AX (33.2 mg AX/kg) markedly attenuated hepatic damage, as shown by the histopathological analysis and reduced levels of plasma biomarkers for hepatic injury. These findings suggest that strategically including antioxidative additives in the sNP/AX has the potential to improve the physicochemical and nutraceutical properties of AX.

Funder

JSPS KAKENHI

Otsuka Toshimi Scholarship Foundation

Publisher

MDPI AG

Subject

Pharmaceutical Science

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