A New Tailored Nanodroplet Carrier of Astaxanthin Can Improve Its Pharmacokinetic Profile and Antioxidant and Anti-Inflammatory Efficacies.

Astaxanthin (ATX) is a carotenoid nutraceutical with poor bioavailability due to its high lipophilicity. We tested a new tailored nanodroplet capable of solubilizing ATX in an oil-in-water micro-environment (LDS-ATX) for its capacity to improve the ATX pharmacokinetic profile and therapeutic efficacy. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to profile the pharmacokinetics of ATX and LDS-ATX, superoxide mutase (SOD) activity to determine their antioxidant capacity, protein carbonylation and lipid peroxidation to compare their basal and lipopolysaccharide (LPS)-induced oxidative damage, and ELISA-based detection of IL-2 and IFN-γ to determine their anti-inflammatory capacity. ATX and LDS-ATX corrected only LPS-induced SOD inhibition and oxidative damage. SOD activity was restored only by LDS-ATX in the liver and brain and by both ATX and LDS-ATX in muscle. While in the liver and muscle, LDS-ATX attenuated oxidative damage to proteins and lipids better than ATX; only oxidative damage to lipids was preferably corrected by LDS-ATX in the brain. IL-2 and IFN-γ pro-inflammatory response was corrected by LDS-ATX and not ATX in the liver and brain, but in muscle, the IL-2 response was not corrected and the IFN-γ response was mitigated by both. These results strongly suggest an organ-dependent improvement of ATX bioavailability and efficacy by the LDS-ATX nanoformulation.

Enhancement of Astaxanthin Bioaccessibility by Encapsulation in Liposomes: An In Vitro Study.

Astaxanthin was encapsulated in liposomes by a thin layer dispersion and ultrasound method using soybean phospholipid. The digestion properties of liposomes for encapsulating astaxanthin were investigated in light of particle size, size distribution, zeta potential, and microstructure during in vitro digestion as a function of time. These results exhibited that the average particle size increased gradually with liposomal vesicles retained round shapes and a fairly uniform distribution after passage through the simulated gastric fluid digestion. The result revealed that astaxanthin-loaded liposomes were stable in low pH conditions. It was also found that the mixed micelles formed in a simulated intestinal fluid. The zeta potential of astaxanthin-loaded liposomes had a decrease in negativity after digestion. In comparison with free astaxanthin, there was an appreciable increase in the bioaccessibility of astaxanthin after encapsulation in liposomes. This enhancement can be attributed to more soluble astaxanthin in the mixed micelles for astaxanthin-loaded liposomes. It indicated that the barrier of the liposomal bilayer could inhibit astaxanthin fading and leaking after encapsulation in liposomes. These results provide useful information for designing more stable delivery systems in the gastrointestinal tract and improving the bioaccessibility of lipophilic nutraceuticals.

Improved intestinal absorption and oral bioavailability of astaxanthin using poly (ethylene glycol)-graft-chitosan nanoparticles: preparation, in vitro evaluation, and pharmacokinetics in rats.

BACKGROUND: Astaxanthin (ASTA) is a kind of food-derived active ingredient (FDAI) with antioxidant and antidiabetic functions. It is nontoxic but its poor solubility and low bioavailability hinder its application in the food industry. In this study, a novel carrier, polyethylene glycol-grafted chitosan (PEG-g-CS) was applied to enhance the bioavailability of astaxanthin. It encapsulated astaxanthin completely by solvent evaporation to manufacture astaxanthin using poly (ethylene glycol)-graft-chitosan nanoparticles (ASTA-PEG-g-CS) nanoparticles to improve absorption. RESULTS: The ASTA-PEG-g-CS nanoparticles were spherical, with a particle size below 200 nm and a ζ potential of about -26 mV. Polyethylene glycol-grafted chitosan can encapsulate astaxanthin well, and the encapsulated astaxanthin was released rapidly - in 15 min in an in vitro release study. In a rat single-pass intestinal perfusion study, a low concentration of ASTA-PEG-g-CS nanoparticle (0.2 µg mL-1 ) was better absorbed in the intestine. In particular, the jejunum could absorb most astaxanthin without a change in the concentration. An in vivo release study also demonstrated that ASTA-PEG-g-CS nanoparticles enhanced oral bioavailability significantly. CONCLUSION: This novel carrier, PEG-g-CS, provided a simple way to encapsulate food, which improved the bioavailability of hydrophobic ingredients. © 2021 Society of Chemical Industry.

"Therapeutic uses of natural astaxanthin: An evidence-based review focused on human clinical trials".

Astaxanthin is a natural C40 carotenoid with numerous reported biological functions, most of them associated with its antioxidant and anti-inflammatory activity, standing out from other antioxidants as it has shown the highest oxygen radical absorbance capacity (ORAC), 100-500 times higher than ⍺-tocopherol and a 10 times higher free radical inhibitory activity than related antioxidants (α-tocopherol, α-carotene, ß -carotene, lutein and lycopene). In vitro and in vivo studies have associated astaxanthin's unique molecular features with several health benefits, including neuroprotective, cardioprotective and antitumoral properties, suggesting its therapeutic potential for the prevention or co-treatment of dementia, Alzheimer, Parkinson, cardiovascular diseases and cancer. Benefits on skin and eye health promotion have also been reported, highlighting its potential for the prevention of skin photo-aging and the treatment of eye diseases like glaucoma, cataracts and uveitis. In this review, we summarize and discuss the currently available evidence on astaxanthin benefits, with a particular focus on human clinical trials, including a brief description of the potential mechanisms of action responsible for its biological activities.

Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent.

Neurological disorders are diseases of the central and peripheral nervous system that affect millions of people, and the numbers are rising gradually. In the pathogenesis of neurodegenerative diseases, the roles of many signaling pathways were elucidated; however, the exact pathophysiology of neurological disorders and possible effective therapeutics have not yet been precisely identified. This necessitates developing multi-target treatments, which would simultaneously modulate neuroinflammation, apoptosis, and oxidative stress. The present review aims to explore the potential therapeutic use of astaxanthin (ASX) in neurological and neuroinflammatory diseases. ASX, a member of the xanthophyll group, was found to be a promising therapeutic anti-inflammatory agent for many neurological disorders, including cerebral ischemia, Parkinson's disease, Alzheimer's disease, autism, and neuropathic pain. An effective drug delivery system of ASX should be developed and further tested by appropriate clinical trials.

Safety assessment of astaxanthin from Haematococcus pluvialis: Acute toxicity, genotoxicity, distribution and repeat-dose toxicity studies in gestation mice.

Natural astaxanthin is the strongest antioxidant ever discovered, with many biological functions, and it is widely used in the fields of health food and biomedical research. In the present study, we aimed to investigate the plasma concentration, distribution and safety of astaxanthin from Haematococcus pluvialis in pregnant mice. In the acute studies, the oral LD50 of astaxanthin was greater than 20 g/kg·bw. In mouse bone marrow micronucleus test, 10 g/kg·bw astaxanthin did not cause damage to chromosomes and mitotic apparatus of pregnant mice. After treatment with a single dose of 500 mg/kg·bw astaxanthin, the concentration of astaxanthin in plasma reached the maximum at 8 h (55.7 µg/L), which was completely metabolized after 48 h. In the repeat-dose toxicity test, 100, 250 and 500 mg/kg·bw astaxanthin showed no abnormalities in terms of body and organ weight as well as hematological and biochemical parameters in clinical observation throughout the pregnancy. During pregnancy, the liver accumulated the highest content of astaxanthin, while the eye exhibited the least. The results indicated that administration of astaxanthin from H. pluvialis throughout pregnancy had no adverse effect on mice.

Absorption and Tissue Distribution of Siphonaxanthin from Green Algae.

Siphonaxanthin has been known to possess inhibitory effects against obesity, inflammation, and angiogenesis. However, little information on its in vivo bioavailability and biotransformation is available. To assess the bioavailability and metabolism of siphonaxanthin, its absorption and accumulation were evaluated using intestinal Caco-2 cells and Institute of Cancer Research (ICR) mice. Siphonaxanthin was absorbed and exhibited non-uniform accumulation and distribution patterns in tissues of ICR mice. Notably, in addition to siphonaxanthin, three main compounds were detected following dietary administration of siphonaxanthin. Because the compounds showed changes on mass spectra compared with that of siphonaxanthin, they were presumed to be metabolites of siphonaxanthin in ICR mice. Siphonaxanthin mainly accumulated in stomach and small intestine, while putative metabolites of siphonaxanthin mainly accumulated in liver and adipose tissues. Furthermore, siphonaxanthin and its putative metabolites selectively accumulated in white adipose tissue (WAT), especially mesenteric WAT. These results provide useful evidence regarding the in vivo bioactivity of siphonaxanthin. In particular, the results regarding the specific accumulation of siphonaxanthin and its metabolites in WAT have important implications for understanding their anti-obesity effects and regulatory roles in lipid metabolism.

Comparative Transcriptome Analyses Provide Potential Insights into the Molecular Mechanisms of Astaxanthin in the Protection against Alcoholic Liver Disease in Mice.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide. It is a complex process, including a broad spectrum of hepatic lesions from fibrosis to cirrhosis. Our previous study suggested that astaxanthin (AST) could alleviate the hepatic inflammation and lipid dysmetabolism induced by ethanol administration. In this study, a total of 48 male C57BL/6J mice were divided into 4 groups: a Con group (fed with a Lieber⁻DeCarli liquid diet), an AST group (fed with a Lieber⁻DeCarli liquid diet and AST), an Et group (fed with an ethanol-containing Lieber⁻DeCarli liquid diet), and a EtAST group (fed with an ethanol-containing Lieber⁻DeCarli liquid diet and AST). Then, comparative hepatic transcriptome analysis among the groups was performed by Illumina RNA sequencing. Gene enrichment analysis was conducted to identify pathways affected by the differentially expressed genes. Changes of the top genes were verified by quantitative real-time PCR (qRT-PCR) and Western blot. A total of 514.95 ± 6.89, 546.02 ± 15.93, 576.06 ± 21.01, and 690.85 ± 54.14 million clean reads were obtained for the Con, AST, Et, and EtAST groups, respectively. Compared with the Et group, 1892 differentially expressed genes (DEGs) (including 351 upregulated and 1541 downregulated genes) were identified in the AST group, 1724 differentially expressed genes (including 233 upregulated and 1491 downregulated genes) were identified in the Con group, and 1718 DEGs (including 1380 upregulated and 338 downregulated genes) were identified in the EtAST group. The enrichment analyses revealed that the chemokine signaling, the antigen processing and presentation, the nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, and the Toll-like receptor signaling pathways enriched the most differentially expressed genes. The findings of this study provide insights for the development of nutrition-related therapeutics for ALD.

Optimization and Formulation of Fucoxanthin-Loaded Microsphere (F-LM) Using Response Surface Methodology (RSM) and Analysis of Its Fucoxanthin Release Profile.

Fucoxanthin has interesting anticancer activity, but is insoluble in water, hindering its use as a drug. Microencapsulation is used as a technique for improving drug delivery. This study aimed to formulate fucoxanthin-loaded microspheres (F-LM) for anticancer treatment of H1299 cancer cell lines and optimize particle size (PS) and encapsulation efficiency (EE). Using response surface methodology (RSM), a face centered central composite design (FCCCD) was designed with three factors: Polyvinylalcohol (PVA), poly(d,l-lactic-co-glycolic acid) (PLGA), and fucoxanthin concentration. F-LM was produced using a modified double-emulsion solvent evaporation method. The F-LM were characterized for release profile, release kinetics, and degradation pattern. Optimal F-LM PS and EE of 9.18 µm and 33.09%, respectively, with good surface morphology, were achieved from a 0.5% (w/v) PVA, 6.0% (w/v) PLGA, 200 µg/mL fucoxanthin formulation at a homogenization speed of 20,500 rpm. PVA concentration was the most significant factor (p < 0.05) affecting PS. Meanwhile, EE was significantly affected by interaction between the three factors: PVA, PLGA, and fucoxanthin. In vitro release curve showed fucoxanthin had a high burst release (38.3%) at the first hour, followed by a sustained release stage reaching (79.1%) within 2 months. Release kinetics followed a diffusion pattern predominantly controlled by the Higuchi model. Biodegradability studies based on surface morphology changes on the surface of the F-LM, show that morphology changed within the first hour, and F-LM completely degraded within 2 months. RSM under FCCCD design improved the difference between the lowest and highest responses, with good correlation between observed and predicted values for PS and EE of F-LM.

Bioaccessibility of Marine Carotenoids.

The benefit of carotenoids to human health is undeniable and consequently, their use for this purpose is growing rapidly. Additionally, the nutraceutical properties of carotenoids have attracted attention of the food industry, especially in a new market area, the 'cosmeceuticals.' Marine organisms (microalgae, seaweeds, animals, etc.) are a rich source of carotenoids, with optimal properties for industrial production and biotechnological manipulation. Consequently, several papers have reviewed the analysis, characterization, extraction and determination methods, biological functions and industrial applications. But, now, the bioaccessibility and bioactivity of marine carotenoids has not been focused of any review, although important achievements have been published. The specific and diverse characteristic of the marine matrix determines the bioavailability of carotenoids, some of them unique in the nature. Considering the importance of the bioavailability not just from the health and nutritional point of view but also to the food and pharmaceutical industry, we consider that the present review responds to an actual demand.

Synthesis, stability and bioavailability of astaxanthin succinate diester.

BACKGROUND: We synthesized astaxanthin succinate diester (ASD), a novel astaxanthin (AST) derivate, with succinic anhydride and free AST. ASD was purified and characterized using silica gel column chromatography and spectrometry, respectively. RESULTS: The ASD final synthesis rate was 82.63%. A stability test revealed a high AST and ASD retention rate at pH 5.0-7.0. ASD showed better stability than did AST under acidic conditions. Both sample ions showed lower retention rates under Fe2+ and Fe3+ states. The ASD metabolic curve showed serum and liver area under the curve from 0 h to time t (AUC0-t ) values of 45.05 ± 4.58 and 120.38 ± 23.66 µg h-1  mL-1 , respectively. The long-term accumulation was significantly higher in the ASD group than in the AST group, which showed higher accumulation in the heart, muscle and spleen than in other tissues in vivo. CONCLUSION: The thermal stability and bioavailability of ASD were higher than that of the non-esterified free AST and common free AST, respectively. Additionally, AST accumulation in different tissues of the ASD group was multifold higher than that of free AST. These results prove that ASD may serve as a better source of AST for human nutrition than does free AST. © 2017 Society of Chemical Industry.

In vitro bioaccessibility of individual carotenoids from persimmon (Diospyros kaki, cv. Rojo Brillante) used as an ingredient in a model dairy food.

BACKGROUND: Addition of persimmon fruit, which is highly rich in carotenoids, to dairy products represents an alternative to obtain functional foods. However, carotenoid bioaccessibility is strongly influenced by fat content and food composition. That is why in vitro bioaccessibility of individual carotenoids was evaluated in persimmon-based dairy products formulated with whole (3.6% fat) or skimmed milk (0.25% fat) and different freeze-dried persimmon tissues. RESULTS: Unambiguous identification of seven xanthophylls (neoxanthin, violaxanthin, antheraxanthin, lutein, zeaxanthin, lutein epoxide and ß-cryptoxanthin) and three hydrocarbon carotenes (α-carotene, ß-carotene and lycopene) was achieved using high-performance liquid chromatography with a reverse-phase C-30 column. Total carotenoid content declined up 71% through the digestion process. In vitro bioaccessibility of carotenoids was significantly higher in dairy products formulated with whole milk than those with skimmed milk, representing a difference of more than 21% (in the formulation using persimmon whole fruit as ingredient). Furthermore, addition of whole milk to any type of persimmon tissue significantly improved the bioaccessibility of total provitamin A carotenoids, reaching the highest values (38%) with whole fruit and whole milk. CONCLUSION: The higher fat content in whole milk exerted a significant influence on carotenoid bioaccessibility, especially when using freeze-dried persimmon whole fruit. © 2017 Society of Chemical Industry.

Preparation of enteric-coated microcapsules of astaxanthin oleoresin by complex coacervation.

Astaxanthin oleoresin (AO) has a number of beneficial physiological functions. However, its sensitivity to light, heat, oxygen and gastric fluids has limited its application. In this paper, we describe the preparation of AO enteric microcapsules by coacervation to improve its stability and enteric solubility, and evaluate their efficacy by measuring the drug loading, encapsulation efficiency, optical microscopic appearance, stability, in vitro release and bioavailability. The results obtained showed that the AO enteric microcapsules possessed a high encapsulation efficiency (85.9%), a satisfactory in vitro release profile, and the ability of the microencapsulated AO to resist the effects of light, heat and oxygen was improved by 2.2-fold, 3.1-fold and 2.4-fold, respectively, during storage. In addition, the bioavailability of AO microcapsules was approximately 1.29-fold higher than AO, which is important for pharmaceutical applications and as a functional food.

Development of a carboxymethyl chitosan functionalized nanoemulsion formulation for increasing aqueous solubility, stability and skin permeability of astaxanthin using low-energy method.

In this research, firstly astaxanthin (ASX)-loaded nanoemulsions (NEs) were produced using a convenient low-energy emulsion phase inversion method. The optimised ASX-NEs were prepared in the presence of Cremophor® EL and Labrafil® M 1944 CS, with a surfactant-to-oil ratio of 4:6. The ASX-NE droplets were spherical with a mean droplet diameter below 100 nm and a small negative surface charge. The system was stable without alteration of mean droplet diameter for three months. Then, the ASX-NE was functionalised with carboxymethyl chitosan (CMCS) through direct CMCS (0.02%) incorporation during the preparation process. The ASX chemical stability and skin permeability increased in the following order: ASX solution control < ASX-NE < CMCS-ASX-NE. Cell viability assays on L929 cells revealed low cytotoxicity of blank NE, ASX-NE and CMCS-ASX-NE in the range from 5 to 500 µg mL-1. In conclusion, the CMCS-ASX-NE might be a promising delivery vehicle in dermal and transdermal products.

Simultaneous Determination of Fucoxanthin and Its Deacetylated Metabolite Fucoxanthinol in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry.

Fucoxanthin and its deacetylated metabolite fucoxanthinol are two major carotenoids that have been confirmed to possess various pharmacological properties. In the present study, fucoxanthinol was identified as the deacetylated metabolite of fucoxanthin, after intravenous (i.v.) and intragastric gavage (i.g.) administration to rats at doses of 2 and 65 mg/kg, respectively, by liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. Next, an accurate and precise LC-MS/MS method was developed to quantitatively determine fucoxanthin and fucoxanthinol in rat plasma. Plasma samples were resolved by LC-MS/MS on a reverse-phase SB-C18 column that was equilibrated and eluted with acetonitrile (A)/aqueous 0.1% formic acid (B; 92/8, v/v) at a flow rate of 0.5 mL/min. Analytes were monitored by multiple-reaction monitoring (MRM) under positive electrospray ionization mode. The precursor/product transitions (m/z) were 659.3→109.0 for fucoxanthin, 617.2→109.0 for fucoxanthinol, and 429.4→313.2 for the internal standard (IS). Calibration curves for fucoxanthin and fucoxanthinol were linear over concentrations ranging from 1.53 to 720 and 1.17 to 600 ng/mL, respectively. The inter- and intraday accuracy and precision were within ±15%. The method was applied successfully in a pharmacokinetic study and the resulting oral fucoxanthin bioavailability calculated.

Assessment of tissue distribution and concentration of ß-cryptoxanthin in response to varying amounts of dietary ß-cryptoxanthin in the Mongolian gerbil.

There is a general lack of knowledge regarding the absorption and tissue storage of the provitamin A carotenoid ß-cryptoxanthin. The present study investigated the whole-body tissue distribution of ß-cryptoxanthin in an appropriate small animal model, the Mongolian gerbil (Meriones unguiculatus), for human provitamin A carotenoid metabolism. After 5 d of carotenoid depletion, five gerbils were euthanised for baseline measurements. The remaining gerbils were placed in three weight-matched treatment groups (n 8). All the groups received 20 µg/d of ß-cryptoxanthin from tangerine concentrate, while the second and third groups received an additional 20 and 40 µg/d of pure ß-cryptoxanthin (CX40 and CX60), respectively, for 21 d. During the last 2 d of the study, urine and faecal samples of two gerbils from each treatment group were collected. ß-Cryptoxanthin was detected in the whole blood, and in twelve of the fourteen tissues analysed. Most tissues resembled the liver, in which the concentrations of ß-cryptoxanthin were significantly higher in the CX60 (17·8 (sem 0·7) µg/organ; P= 0·004) and CX40 (16·2 (sem 0·9) µg/organ; P= 0·006) groups than in the CX20 group (13·3 (sem 0·4) µg/organ). However, in intestinal tissues, the concentrations of ß-cryptoxanthin increased only in the CX60 group. Despite elevated vitamin A concentrations in tissues at baseline due to pre-study diets containing high levels of vitamin A, ß-cryptoxanthin maintained those vitamin A stores. These results indicate that ß-cryptoxanthin is stored in many tissues, potentially suggesting that its functions are widespread.

In vitro investigation of the bioaccessibility of carotenoids from raw, frozen and boiled red chili peppers (Capsicum annuum).

BACKGROUND: Carotenoid-rich foods are associated with antioxidant activity and the ability to alleviate chronic diseases. PURPOSE: The present study investigated the effect of processing on the content and bioaccessibility of carotenoids from 13 cultivars of red chili pepper (Capsicum annuum). METHODS: Carotenoids in chili peppers were analyzed before an in vitro digestion process. The portion of carotenoid transferred to the micelle fraction (bioaccessibility) was also quantified. RESULTS: ß-Carotene, ß-cryptoxanthin, capsanthin and antheraxanthin were the most abundant carotenoids. Zeaxanthin, violaxanthin, neoxanthin and lutein were detected at lower concentrations. In general, freezing and boiling reduced carotenoid contents. Capsanthin and zeaxanthin had the highest bioaccessibility at an average value from 36 to 40%, followed by antheraxanthin (26%). Bioaccessibility of ß-cryptoxanthin, violaxanthin and ß-carotene was lower, averaging 6.1, 4.8 and 4.0%, respectively. Neoxanthin and lutein were not detected in micelles. Freezing increased the bioaccessibility of capsanthin, zeaxanthin, antheraxanthin, ß-cryptoxanthin and violaxanthin; ß-cryptoxanthin bioaccessibility increased and capsanthin and zeaxanthin bioaccessibility decreased following boiling. CONCLUSIONS: Differences in the contents and bioaccessibility of carotenoids in 13 C. annuum cultivars and between the processed methods were herein evidenced.

Astaxanthin: sources, extraction, stability, biological activities and its commercial applications--a review.

There is currently much interest in biological active compounds derived from natural resources, especially compounds that can efficiently act on molecular targets, which are involved in various diseases. Astaxanthin (3,3'-dihydroxy-ß, ß'-carotene-4,4'-dione) is a xanthophyll carotenoid, contained in Haematococcus pluvialis, Chlorella zofingiensis, Chlorococcum, and Phaffia rhodozyma. It accumulates up to 3.8% on the dry weight basis in H. pluvialis. Our recent published data on astaxanthin extraction, analysis, stability studies, and its biological activities results were added to this review paper. Based on our results and current literature, astaxanthin showed potential biological activity in in vitro and in vivo models. These studies emphasize the influence of astaxanthin and its beneficial effects on the metabolism in animals and humans. Bioavailability of astaxanthin in animals was enhanced after feeding Haematococcus biomass as a source of astaxanthin. Astaxanthin, used as a nutritional supplement, antioxidant and anticancer agent, prevents diabetes, cardiovascular diseases, and neurodegenerative disorders, and also stimulates immunization. Astaxanthin products are used for commercial applications in the dosage forms as tablets, capsules, syrups, oils, soft gels, creams, biomass and granulated powders. Astaxanthin patent applications are available in food, feed and nutraceutical applications. The current review provides up-to-date information on astaxanthin sources, extraction, analysis, stability, biological activities, health benefits and special attention paid to its commercial applications.

Comparative Pharmacokinetic Study of Standard Astaxanthin and its Micellar Formulation in Healthy Male Volunteers.

BACKGROUND AND OBJECTIVE: Astaxanthin is a naturally occurring carotenoid with high anti-oxidant properties, but it is a very lipophilic compound with low oral bioavailability. This study was conducted to compare the pharmacokinetic parameters of a novel astaxanthin preparation based on micellar solubilization technology, NovaSOL® 400-mg capsules (Test product), and those of astaxanthin 400-mg capsules (reference product), after single oral dose administration to healthy male adults. METHODS: A single oral dose (400 mg equivalent to 8 mg astaxanthin) of test and reference astaxanthin were administered with 240 mL of water to 12 volunteers according to crossover design, in two phases, with a washout period of 1 week in between. Blood samples were collected at hourly intervals for the first 12 h, then at 24.0, 48.0, and 72.0 h after administration. Aliquots of plasma were centrifuged and the clear supernatant was injected into the high performance liquid chromatography-diode array detection (HPLC-DAD) system. Plasma concentration of astaxanthin versus time profiles were constructed, and the primary pharmacokinetic parameters, maximum concentration (Cmax), area under concentration time curve from time of administration (0) to time (t) [AUC0-t] or to infinity ∞, [AUC0-∞],  half-life (T½) and time to reach Cmax (Tmax) were calculated. RESULTS: The test micellar astaxanthin reached a Cmax of 7.21 µg/ml after 3.67 h compared to only 3.86 µg/ml after 8.5 h for the reference native astaxanthin. CONCLUSION: Micellar formulation of astaxanthin is capable of producing a high concentration of astaxanthin in plasma in a shorter time, thereby expected to provide faster potential therapeutic efficacy.

Effect of type of TAG fatty acids on lutein and zeaxanthin bioavailability.

The xanthophylls lutein and zeaxanthin probably play a role in visual function and may participate in the prevention of age-related eye diseases. Although a minimum amount of TAG is required for an optimal bioavailability of these carotenoids, the effect of the type of TAG fatty acids (FA) is less clear. The aim was to assess the effect of the type of TAG FA on bioavailability of these xanthophylls. A total of three complementary models were used: an in vitro digestion model to study bioaccessibility, Caco-2 cells to study uptake efficiency and orally administered rats to study in vivo bioavailability. Results showed that lutein and zeaxanthin bioaccessibility was greater (about 20-30 %, P< 0·05) with butter and palm oil than with olive and fish oils. Mixed micelle size, which was significantly lower (about 8 %, P< 0·05) with SFA than with unsaturated FA, was inversely related to lutein and zeaxanthin bioaccessibility. There was no significant effect of the type of TAG FA on xanthophyll uptake by Caco-2 cells, but some compounds present in natural oils significantly affected xanthophyll uptake. Oral administration of rats with spinach and butter over 3 d led to a higher fasting plasma lutein concentration than oral administration with olive or fish oils. In conclusion, dietary fats rich in SFA lead to a higher bioavailability of lutein and zeaxanthin, as compared with fats rich in MUFA and PUFA. This is due partly to the higher bioaccessibility of these xanthophylls in the smaller mixed micelles produced when SFA are incorporated into mixed micelles.