Enhanced oral bioavailability of a sterol-loaded microemulsion formulation of Flammulina velutipes, a potential antitumor drug

Abstract

Purpose:To investigate the growth inhibition activity of Flammulina velutipes sterol (FVS) against certain human cancer cell lines (gastric SGC and colon LoVo) and to evaluate the optimum microemulsion prescription, as well as the pharmacokinetics of encapsulated FVS. Methods: Molecules present in the FVS isolate were identified by gas chromatography/mass spectrometry analysis. The cell viability of FVS was assessed with methyl thiazolyl tetrazolium (MTT) bioassay. Based on the solubility study, phase diagram and stability tests, the optimum prescription of F. velutipes sterol microemulsions (FVSMs) were determined, followed by FVSMs characterization, and its in vivo pharmacokinetic study in rats. ). The optimal FVSMs prescription consisted of 3.0% medium chain triglycerides, 5.0% ethanol, 21.0% Cremophor EL and 71.0% water (w/w) with associated solubility of FVS being 0.680 mg ⋅ mL −1 as compared to free FVS (0.67 µg ⋅ mL −1 ). The relative oral bioavailability (area-under-the-curve values of ergosterol and 22,23-dihydroergosterol showed a 2.56-fold and 4.50-fold increase, respectively) of FVSMs (mean diameter ∼ 22.9 nm) as against free FVS were greatly enhanced. Our laboratory has been able to screen out lipid soluble sterols with an antitumor effect from F. velutipes by lipidraft chromatography, which was found to be linked to the tyrosine kinase receptor (data not published). In this study, our laboratory was interested in performing a preliminary investigation of the anticancer potential and bioavailability of F. velutipes sterol (FVS) as an in-depth contribution to the research of F. velutipes. FVS is a white powder, which can easily dissolve in ether, chloroform, hot ethanol, and other organic solvents, but barely dissolves in water. As a result, it is necessary to find a method to improve the solubility and oral bioavailability of this sterol. Dovepress 5067 O R I G I N A L R E S E A R C HMicroemulsions are thermodynamically stable nanometer systems with characteristics of easy preparation, small droplet size, low viscosity, and strong solubilization effect. 12It is formed spontaneously by water, oil, surfactant and cosurfactant. 13,14 According to the structure of a microemulsion, it can be divided into water-in-oil (w/o), oil-in-water (o/w) and bicontinuous microemulsion. 15 As a drug carrier, a microemulsion can increase the solubility and oral bioavailability of poorly soluble drugs, ameliorate the localization, improve systemic delivery of the drug, and possess the ability of targeting drug release. [16][17][18] The absolute bioavailability of a poorly soluble drug cyclosporin A which was loaded into a microemulsion system was increased to about 3.3-and 1.25-fold compared with free Sandimmun and Sandimmun Neoral (Novartis, Basel, Switzerland), which were used as commercial cyclosporin A. 19 In addition, it has been confirmed that the microemulsion system containing the poorly soluble drug docetaxel could improve the solubilization property and oral bioavailability of the drug. 20 Presently, there a...

Golden Needle Mushroom: A Culinary Medicine with Evidenced-Based Biological Activities and Health Promoting Properties

“…Thus, F. velutipes may represent an important food source for humans or other animals to obtain sufficient amounts of the essential fatty acids our body requires but which cannot be synthesized. Many studies also demonstrated that sterols extracted from F. velutipes possess antiproliferative activity against several cancer cell lines and have the potential to be developed as chemotherapeutic agents (Yi et al, 2012, 2013a); while mycosterol, derived from the extract of F. velutipes , exhibits potent hypolipidemic activity (Yeh et al, 2014). …”

“…It showed potent antiproliferative activity against human SGC cells (stomach cancer cells) with an IC 50 of 11.99 μg/mL, HepG-2 cells with IC 50 at 9.3 μg/mL, A549 lung cancer cell with IC 50 at 20.4 μg/mL and U251 glioblastoma with IC 50 at 23.42 μg/mL (Yi et al, 2012, 2013a,b). Studies have also been done to improve the bioavailability, biodistribution and solubility of sterols from F. velutipes through encapsulation in liposomes, mixed micelles nanoformulation and microemulsion (Yi et al, 2012, 2013a,b). …”

Combining transcriptomics and metabolomics to reveal the underlying molecular mechanism of ergosterol biosynthesis during the fruiting process of Flammulina velutipes

“…Flammulina velutipes ( F. velutipes ) has been recognized as a model industrial basidiomycete; it is one of the most commonly used edible fungi, serving as an excellent source of vitamins, amino acids, polysaccharides, fibre, terpenoids, phenolic acids, steroids, fatty acids and other metabolites, and is widely cultivated worldwide [2–5]. Compounds with pharmaceutical value can be isolated from the fruiting bodies or mycelia of F. velutipes , including anti-inflammatory and immunomodulatory proteins [6], antitumour, antioxidant and acetylcholinesterase inhibitory polysaccharides, antitumour agglutinins and immunomodulatory compounds [7], antimicrobial terpenoids [8], and antitumour and antioxidant sterols [9, 10]. The active antitumour sterols include ergosterol, 22,23-dihydroergosterol, ergosta-5,8,22-trien-3-ol and ergo-8(14)-ene-3-ol [11, 12].…”

“…The active antitumour sterols include ergosterol, 22,23-dihydroergosterol, ergosta-5,8,22-trien-3-ol and ergo-8(14)-ene-3-ol [11, 12]. The chemical composition of sterols is mainly ergosterol (54.8%) and 22,23-dihydroergosterol (27.9%) [10]. GC-MS or HPLC studies of saponification extraction have revealed that the ergosterol content in F. velutipes was 35.5 mg/100 g in wet weight or 68.0 mg/100 g in dry weight [13, 14].…”