In human mammary epithelial cells (MCF10A), (E/Z)-Squalene (0-50 μM) lowers intracellular ROS levels, inhibits H2O2-induced oxidative damage, and shields cells from DNA oxidative damage [1].

Absorption, Distribution and Excretion
Squalene is used in the oil phase of some emulsion vaccine adjuvants, but its metabolic process as a vaccine component after intramuscular injection in humans remains unclear. This study constructed a physiologically based pharmacokinetic (PBPK) model to simulate tissue distribution after intramuscular injection of squalene in water-in-oil (SQ/W) emulsion, to quantitatively assess the tissue distribution of squalene in humans after a single intramuscular injection. The PBPK model incorporated relevant physicochemical properties of squalene; estimation of the SQ/W emulsion lysis time course; anatomical and physiological parameters of the injection site and surrounding tissues; and local preferential lymphatic transport. The model predicted that the squalene would be cleared from the deltoid muscle within six days after a single intramuscular injection of the SQ/W emulsion. Most of the injected squalene would be distributed to draining lymph nodes and adipose tissue. The model indicated that squalene decayed slowly in the latter compartment, likely due to its partitioning into neutral lipids and lower biotransformation in that compartment. Parallel pharmacokinetic modeling of mouse muscle showed that the kinetics of the SQ/W emulsion were consistent with the immunokinetic time course of previously reported commercial squalene-containing adjuvants in this species. In summary, this study provides important pharmacokinetic predictions regarding the metabolism of squalene-containing emulsions in humans. These findings may contribute to understanding the immunokinetics of this type of novel vaccine adjuvant and may aid in future quantitative risk analyses incorporating mechanisms of action data. More than 60% of ingested squalene is absorbed in the small intestine; it then enters systemic circulation via the lymphatic system in the form of chylomicrons. In the blood, squalene is primarily carried by very low-density lipoproteins and distributed to various tissues throughout the body. Most squalene is distributed to the skin. Animal studies have shown that squalene is slowly absorbed through the skin, while both squalane and squalene have very low absorption rates in the gastrointestinal tract. Metabolism/Metabolites This review summarizes the oxidation process of squalene, a unique human compound produced by sebaceous glands. This chemical transformation has important effects at multiple levels. Squalene byproducts, primarily in the form of peroxides, can lead to acne formation, promote inflammatory acne, and potentially alter skin texture (wrinkles). This paper elucidates the experimental conditions for oxidative and/or photo-oxidative mechanisms, suggesting they may serve as biomarkers of the effects of air pollution on the skin. Ozone, long-wave UVA rays, and cigarette smoke have been identified as strong oxidants of squalene. This paper presents several in vitro, ex vivo, and in vivo experiments as examples to investigate ingredients or products that can enhance or counteract such chemical changes, which generally have adverse effects on various skin tissues. This study employed proton transfer reaction mass spectrometry (PTR-MS) for direct air analysis of volatile products generated from the reaction of ozone with human skin lipids. A series of small-scale in vitro and in vivo experiments were first conducted, followed by experiments on human subjects in a simulated office environment. The latter used actual ozone mixing ratios (approximately 15 ppb with human presence). Detected products included monofunctional and bifunctional compounds containing carbonyl, carboxyl, or α-hydroxy ketone groups. Three previously unreported dicarbonyl compounds were identified, and two previously unreported α-hydroxy ketones were preliminarily identified. The compounds detected in this study (excluding acetone) have been overlooked in previous indoor pollutant surveys, reflecting the limitations of current routine analytical methods used to monitor indoor air. The results are in perfect agreement with the Krich mechanism, which describes the reaction of ozone with squalene (the most abundant monounsaturated component in skin lipids) and several free or esterified forms of unsaturated fatty acids. Quantitative product analysis confirmed that squalene is a major ozone scavenger at the interface between indoor air and the human body envelope. The reaction of ozone with human skin lipids reduces the mixing ratio of ozone in indoor air but increases the mixing ratio of volatile products and may increase the concentration of low-volatility products on the skin surface. Some volatile products, particularly dicarbonyl compounds, may be respiratory irritants. Some low-volatility products may be skin irritants. Squalene is metabolized to cholesterol.

[1]. Current Insights into the Biological Action of Squalene. Mol Nutr Food Res. 2018 Jun 8:e1800136.

Trans-squalene is a clear, slightly yellow liquid with a faint odor. Its density is 0.858 g/cm³. Squalene is a triterpenoid compound composed of 2,6,10,15,19,23-hexamethyltetracosane, with double bonds at positions 2, 6, 10, 14, 18, and 22, all in an all-E configuration. It is a human metabolite, a plant metabolite, a Saccharomyces cerevisiae metabolite, and a mouse metabolite. Squalene was originally extracted from shark liver oil. It is a natural 30-carbon isoprene compound and an intermediate metabolite in cholesterol synthesis. It is not prone to lipid peroxidation and has skin-protective properties. Squalene is widely distributed in human tissues, typically bound to very low-density lipoproteins, and transported in serum. Squalene is being investigated as an adjuvant therapy for cancer.
Squalene has been reported to exist in red algae (Erythrophleum fordii), hybrid amaranth (Amaranthus hybridus), and other organisms with relevant data.
Squalene is a metabolite of Saccharomyces cerevisiae, produced by or present in the yeast.
It is a naturally occurring 30-carbon triterpenoid.
See also: olive oil (one of its components); shark liver oil (one of its components).
Mechanism of Action

Squalene is an isoprene compound with a structure similar to β-carotene and is an intermediate metabolite in cholesterol synthesis. Approximately 60% of dietary squalene is absorbed in the human body. It is typically bound to very low-density lipoprotein, transported in serum, and widely distributed in human tissues, with the highest concentration in the skin, where it is a major component of skin surface lipids. Squalene is not prone to peroxidation and appears to act as a quencher of singlet oxygen in the skin, protecting the skin surface from lipid peroxidation damage caused by ultraviolet radiation and other ionizing radiation. Squalene supplementation in mice significantly enhanced their cellular and nonspecific immune functions in a dose-dependent manner. Squalene may also act as a "scavenger" of highly lipophilic exogenous substances. Due to its nonpolar nature, it has a higher affinity for non-ionized drugs. In animal studies, dietary squalene supplementation lowered cholesterol and triglyceride levels. In humans, squalene may help enhance the efficacy of certain cholesterol-lowering drugs. Currently, the primary therapeutic use of squalene is as adjuvant therapy for various cancers. Although epidemiological, experimental, and animal evidence suggests its anticancer properties, no human trials have yet been conducted to verify the role of this nutrient in cancer treatment regimens.
Based on the previous discovery that coproporphyrin secreted by Propionibacterium acnes can produce singlet oxygen, we hypothesized that singlet oxygen generated under ultraviolet irradiation would promote the peroxidation of lipids on the skin surface. We found that under ultraviolet irradiation, coproporphyrin-derived singlet oxygen effectively oxidized squalene, and the rate constant of squalene peroxidation was ten times higher than that of other skin surface lipids tested. UVA promoted this response more effectively than UVB. Furthermore, we found that topical application of squalene peroxide induced hyperpigmentation by increasing the release of prostaglandin E2 from guinea pig keratinocytes. These results suggest that squalene peroxide, formed from singlet oxygen, plays a crucial role in photoinduced skin damage.

C30H50

410.72

410.391

7683-64-9

638072

Oil; crystals from ether/methanol (-5 °C)

0.8±0.1 g/cm3

429.3±0.0 °C at 760 mmHg

-75ºC(lit.)

254.1±22.2 °C

0.0±0.5 mmHg at 25°C

1.492

13.09

0

0

15

30

578

0

C/C(C)=C\CC/C(C)=C/CC/C(C)=C/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)\C

YYGNTYWPHWGJRM-AAJYLUCBSA-N

InChI=1S/C30H50/c1-25(2)15-11-19-29(7)23-13-21-27(5)17-9-10-18-28(6)22-14-24-30(8)20-12-16-26(3)4/h15-18,23-24H,9-14,19-22H2,1-8H3/b27-17+,28-18+,29-23+,30-24+

(6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)