title: Formulation, biological and pharmacokinetic studies of sucrose ester-stabilized nanosuspensions of oleanolic Acid.
abstract: OBJECTIVE
  The aim of this study was to develop sucrose ester (SE)-stabilized oleanolic acid (OA) nanosuspensions (NS) for enhanced delivery.
  
  
  METHODS
  SEOA NS were prepared via O/W emulsion and organic solvent evaporation methods. The particles' size and polydispersity index were measured by nanosizer. Their percent encapsulation efficiency, saturation solubility and in vitro dissolution rate were obtained via HPLC. The in vitro bioefficacy was analyzed by MTT measurements in A549 human non-small-cell lung cancer cell line. The cellular uptake of OA and in vivo pharmacokinetics profile were determined using LC-ESI-MS/MS.
  
  
  RESULTS
  Spherical SEOA NS particles (~100 nm in diameter) were produced and found to be physicochemically stable over a month at 4°C. In particular, SEOA 4121 NS (SEL: SEP at 4:1 w/w; SE: OA at 2:1 w/w) produced the greatest increase in saturation solubility (1.89 mg/mL vs. 3.43 μg/mL), dissolution rate, cytotoxicity and bioavailability. Preliminary studies indicated that cellular uptake of SEOA NS by A549 cells was temperature-, concentration- and time-dependent.
  
  
  CONCLUSIONS
  Preparing OA as SE-stabilized NS particles provides a novel method to enhance saturation solubility, in vitro dissolution rate, bioefficacy and in vivo bioavailability of free OA and/or other potentially useful hydrophobic drugs.
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Wenji
authors.initials: W
authors.lastname: Li
authors.forename: Surajit
authors.initials: S
authors.lastname: Das
authors.forename: Ka-yun
authors.initials: KY
authors.lastname: Ng
authors.forename: Paul W S
authors.initials: PW
authors.lastname: Heng
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D005079:Excipients / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D009828:Oleanolic Acid / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D010316:Particle Size; D012995:Solubility; D013395:Sucrose / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D004655:Emulsions; D004952:Esters; D005079:Excipients; D013395:Sucrose; D009828:Oleanolic Acid