title: Preparation, characterization, and in vivo pharmacokinetics of nanostructured lipid carriers loaded with oleanolic acid and gentiopicrin.
abstract: BACKGROUND
  The purpose of this work was to develop nanostructured lipid carriers (NLCs) loaded simultaneously with oleanolic acid and gentiopicrin.
  
  
  METHODS
  An aqueous dispersion of NLCs was prepared successfully using a film-ultrasonic method, with glycerin monostearate as the solid lipid and oleic acid as the liquid lipid. Poloxamer 188 was used as the surfactant. A central composite design was used to optimize the technologic parameters. The characteristics of the NLCs were then investigated.
  
  
  RESULTS
  The encapsulation efficiency was 48.34% ± 2.76%, drug loading was 8.06% ± 0.42%, particle size was 111.0 ± 1.56 nm, polydispersity index was 0.287 ± 0.01, and zeta potential was -23.8 ± 0.36 mV for the optimized NLCs. The other physicochemical properties were characterized by transmission electron microscopy and differential scanning calorimetry. Drug release followed first-order kinetics and release studies confirmed that oleanolic acid and gentiopicrin fitted a sustained-release model. Compared with NLCs loaded with oleanolic acid or gentiopicrin alone, NLCs loaded with both oleanolic acid and gentiopicrin produced drug concentrations which persisted for a significantly longer time in plasma, with a linear decrement following second-order kinetics. Aspartate and alanine aminotransferase levels were significantly lower on exposure to NLCs loaded with both oleanolic acid and gentiopicrin than in negative controls.
  
  
  CONCLUSIONS
  The results of this study confirm that oleanolic acid and gentiopicrin can be loaded simultaneously into NLCs. Compared with oleanolic acid and gentiopicrin loaded alone, sustained release and protective effects against hepatic injury were observed using NLCs loaded with both oleanolic acid and gentiopicrin.
authors.affiliation: School of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Kunchi
authors.initials: K
authors.lastname: Zhang
authors.forename: Shaowa
authors.initials: S
authors.lastname: Lv
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Li
authors.forename: Yufei
authors.initials: Y
authors.lastname: Feng
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.forename: Yongji
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D005260:Female; D057888:Iridoid Glucosides / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D009828:Oleanolic Acid / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D057888:Iridoid Glucosides; D008055:Lipids; C012997:gentiopicroside; D009828:Oleanolic Acid; D002251:Carbon Tetrachloride
keywords: central composite design; in vitro release; nanostructured lipid carriers; pharmacokinetics