Phytosterols, also known as plant sterols, are a type of steroidal compound. They are widely found in vegetables, fruits, beans, nuts, grains and other plants. They have outstanding lipid-lowering, anti-oxidation, anti-inflammatory, cancer cell proliferation inhibition, skin barrier repair, skin soothing and other functions, and are often used in food health care, cosmetics, medicine, agriculture and animal husbandry. However, phytosterols have poor water solubility and fat solubility, which greatly limits their application. Therefore, researchers generally choose to synthesize phytosterols into phytosterol esters that are more soluble in oil phase or encapsulate them in liposome nanocarriers before applying them. Phytosterols (esters) are a type of bridged ring compound composed of multiple aliphatic six-membered rings and five-membered rings. The main skeleton structure is a cyclopentane octahydrophenanthrene skeleton, also known as the "steroidal skeleton". Steroidal compounds usually exist in three forms: sterols, alkanoic acid sterols or glycosides. Among them, under saponification conditions, alkanoic acid esters and glycosides will decompose into free phytosterols. The carbon number 3 of sterol is connected to the alcohol hydroxyl group and the carbon number 17 is connected to different substituents R. It will form various types due to the stereoisomerism of the carbon atom of the alcohol hydroxyl group and the different substituents R2. Whether the carbon number 5 is saturated determines whether it is a sterol or a stanol. The five common sterols are β-sitosterol, stigmasterol, campestanol, campesterol and cholesterol. Among them, the first four are phytosterols, and the fifth is cholesterol. When the alcohol hydroxyl group of carbon number 3 undergoes esterification reaction with fatty acids, the corresponding phytosterol esters are formed. For example, it combines with oleic acid to form phytosterol oleate.
Figure 1. Structure of phytosterols.(Matsuoka R. 2022)
Existing studies have found that plant sterols (esters) have the following properties: 1. Lowering cholesterol: A large number of medical clinical experiments, experiments on hyperlipidemia mice and human trials on volunteers have shown that plant sterols (esters) have the effect of lowering cholesterol and blood lipids. Related mechanism studies have shown that plant sterols reduce the body's intake of cholesterol by competing with cholesterol for absorption in the stomach and intestines. 2. Anti-inflammatory effect: Existing reports have shown that many plant sterol esters have anti-inflammatory effects. Studies have found that plant sterols can effectively reduce the secretion of inflammatory factors. 3. Reduce the risk of colon cancer: Researchers have found that a plant cell metabolite can effectively inhibit the proliferation of human HT-29 colon cancer cells. Material analysis shows that plant sterol esters play a role in it. 4. High melting point and low solubility: In order to solve the difficulty of application, researchers have carried out various physical and chemical modifications on plant sterols. Physical modifications include microemulsification and self-emulsification, microencapsulation, biopolymer-based, surfactant-based and lipid-based nanocarriers, etc. Chemical modifications include esterification, ethoxylation, and polyethylene glycol (PEG) modification, which respectively increase the fat solubility and water solubility of phytosterols. 5. Safety: Phytosterols are safe for the human body, but the safety of modified phytosterols is not absolutely safe. Regarding the above-mentioned physical and chemical modifications, researchers found that phytosterol esters are considered safe, but phytosterol oxides that may be produced during the synthesis process show toxicity in animal models.
The Cosmetic Ingredient Review (CIR) reports 26 phytosterol and phytosterol ester ingredients for use in cosmetics. These ingredients are used in cosmetics as skin conditioners, hair conditioners, viscosity enhancers, skin protectants, antioxidants, pharmaceutical preservatives and fragrances. Relevant toxicological data show that phytosterols (esters) are safe. The U.S. Food and Drug Administration (FDA) reports on the application of phytosterols (esters) in cosmetics as follows: All cosmetic categories use phytosterols (esters) except baby products. Of the 66 sterol raw materials used, about 36 are phytosterol raw materials, and the rest are cholesterol raw materials. Cholesterol is an essential substance for the human body and plays an important role in maintaining skin health. However, when it is applied directly to the skin, it may cause inflammation and acne. In contrast, phytosterols and their esters are well tolerated by the skin and can mimic the functions of cholesterol. Another issue worth noting is that cholesterol only exists in animals and its synthesis process is quite complicated with nearly 30 steps of reaction. Therefore, it is extracted from the spinal cord of cattle or from lanolin, which is the most common way to obtain commercial cholesterol. In terms of source, it is not as safe, environmentally friendly and sustainable as phytosterols. Studies have found that phytosterols can have a proliferation effect on fibroblasts, promote the production of collagen, and have an inhibitory effect on melanocytes in cosmetics. In addition, phytosterols also show UV protection, moisturizing, anti-oxidation, anti-inflammatory, and hair growth effects, which allows it to inhibit skin inflammation, repair skin barriers, slow down skin itching, prevent skin aging, improve skin elasticity, and reduce skin roughness.
Alternate Names:
Liposome-Encapsulated Phytosterol
Phytosterol Liposomes
Phytosterol Nanocarriers
References:
1. Matsuoka R. Property of Phytosterols and Development of Its Containing Mayonnaise-Type Dressing. Foods. 2022, 11(8):1141.
Phytosterol-loaded CD44 receptor-targeted PEGylated nano-hybrid phyto-liposomes for synergistic chemotherapy
Expert Opin Drug Deliv.
Authors: Gautam M, Thapa RK, Gupta B, Soe ZC, Ou W, Poudel K, Jin SG, Choi HG, Yong CS, Kim JO.
Abstract
Background: Phytosterols significantly reduce the risk of cancer by directly inhibiting tumor growth, inducing apoptosis, and inhibiting tumor metastasis. Stigmasterol (STS), a phytosterol, exhibits anticancer effects against various cancers, including breast cancer. Chemotherapeutics, including doxorubicin (DOX), might act synergistically with phytosterol against the proliferation and metastasis of breast cancer. Although such compounds can show potential anticancer activity, their combined effect with suitable formulation has not investigated yet.Methods: Hyaluronic acid (HA)-modified PEGylated DOX-STS loaded phyto-liposome was fabricated via a thin-film hydration method. The prepared phyto-liposome was optimized with regards to its physicochemical and other properties. Further, in vitro and in vivo study was carried out in breast cancer cells expressing a different level of CD44 receptors.Results: The particle size of prepared HA-DOX-STS-lipo was 173.9 ± 2.4 nm, and showed pH-depended DOX release, favoring the effective tumor targetability. The in vitro anticancer activity of HA-DOX-STS-lipo was significantly enhanced in MDA-MB-231, CD44-overexpressing cells relative to MCF-7 cells demonstrating HA-mediated targeting effect. HA-DOX-STS-lipo accumulated more and increased antitumor efficacy in the MDA-MB-231 xenograft tumor model expressing high levels of CD44, suggesting the potential of carrier system toward CD44-overexpressing tumors.
Carboxylated phytosterol derivative-introduced liposomes for skin environment-responsive transdermal drug delivery system
J Liposome Res.
Authors: Yamazaki N, Yamakawa S, Sugimoto T, Yoshizaki Y, Teranishi R, Hayashi T, Kotaka A, Shinde C, Kumei T, Sumida Y, Shimizu T, Ohashi Y, Yuba E, Harada A, Kono K.
Abstract
Transdermal drug delivery systems are a key technology for skin-related diseases and for cosmetics development. The delivery of active ingredients to an appropriate site or target cells can greatly improve the efficacy of medical and cosmetic agents. For this study, liposome-based transdermal delivery systems were developed using pH-responsive phytosterol derivatives as liposome components. Succinylated phytosterol (Suc-PS) and 2-carboxy-cyclohexane-1-carboxylated phytosterol (CHex-PS) were synthesized by esterification of hydroxy groups of phytosterol. Modification of phytosterol derivatives on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes was confirmed by negatively zeta potentials at alkaline pH and the change of zeta potentials with decreasing pH. In response to acidic pH and temperatures higher than body temperature, Suc-PS-containing and CHex-PS-containing liposomes exhibited content release at intracellular acidic compartments of the melanocytes at the basement membrane of the skin. Phytosterol-derivative-containing liposomes were taken up by murine melanoma-derived B16-F10 cells. These liposomes delivered their contents into endosomes and cytosol of B16-F10 cells. Furthermore, phytosterol-derivative-containing liposomes penetrated the 3 D skin models and reached the basement membrane. Results show that pH-responsive phytosterol-derivative-containing DMPC liposomes are promising for use in transdermal medical or cosmetic agent delivery to melanocytes.
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