title: Enhanced oral bioavailability of a sterol-loaded microemulsion formulation of Flammulina velutipes, a potential antitumor drug.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  The chemical composition of FVS was mainly ergosterol (54.8%) and 22,23-dihydroergosterol (27.9%). After 72 hours of treatment, both the FVS (half-maximal inhibitory concentration [IC(50)] = 11.99 μg · mL(-1)) and the standard anticancer drug, 5-fluorouracil (IC(50) = 0.88 μg · mL(-1)) exhibited strong in vitro antiproliferative activity against SGC cells, with IC(50) > 30.0 μg · mL(-1); but the FVS performed poorly against LoVo cells (IC(50) > 40.0 μg · mL(-1)). 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.
  
  
  CONCLUSIONS
  These results indicate that the FVS could be a potential candidate for the development of an anticancer drug and it is readily bioavailable via microemulsion formulations.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, People's Republic of China.
authors.forename: Chengxue
authors.initials: C
authors.lastname: Yi
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.forename: Shanshan
authors.initials: S
authors.lastname: Tong
authors.forename: Xia
authors.initials: X
authors.lastname: Cao
authors.forename: Caleb K
authors.initials: CK
authors.lastname: Firempong
authors.forename: Hongfei
authors.initials: H
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Fu
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Yingshu
authors.initials: Y
authors.lastname: Feng
authors.forename: Huiyun
authors.initials: H
authors.lastname: Zhang
authors.forename: Ximing
authors.initials: X
authors.lastname: Xu
authors.forename: Jiangnan
authors.initials: J
authors.lastname: Yu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents; D001682:Biological Availability; D045744:Cell Line, Tumor; D004655:Emulsions; D055393:Flammulina / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013261:Sterols / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D013261:Sterols