title: Preparation, optimization, characterization and in vivo pharmacokinetic study of asiatic acid tromethamine salt-loaded solid lipid nanoparticles.
abstract: OBJECTIVE
  To enhance the oral bioavailability of asiatic acid tromethamine salt (AAS) by encapsulation in solid lipid nanoparticles (SLN).
  
  
  METHODS
  The AAS-loaded SLN (AASLN) was prepared by the modified solvent injection method with glycerin monostearate (GMS) as lipid and poloxamer 188 as surfactant. A Box-Behnken design was used to optimize the formulations. Physicochemical characterization was carried out by using dynamic light scattering, scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Stabilities at 4 °C and pH 1.2 were investigated by particle size or/and entrapment efficiency (EE%). The in vivo pharmacokinetics was evaluated by HPLC-MS/MS.
  
  
  RESULTS
  The optimal formulation of AASLN had an average size of 237 nm with zeta potential of -35.9 mV, and EE% of 64.4%. SEM showed that the AASLN had spherical shape with smooth surface. Furthermore, DSC and X-ray analyses indicated that AAS was amorphous state and the crystal degree of GMS was significantly decreased in the formulation. AASLN showed excellent stability at 4 °C for 1 month and no coacervation at pH 1.2. The bioavailability of AAS in SLN was found to be 2.5-fold higher than that of AAS alone after a single oral administration in rats.
  
  
  CONCLUSIONS
  This study reveals that SLN is developed as a promising oral delivery system of AAS with significantly enhanced bioavailability and good storage stability.
authors.affiliation: a National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry , Shanghai , People's Republic of China ;|b Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry , Shanghai , People's Republic of China.
authors.forename: Gu
authors.initials: G
authors.lastname: Lingling
authors.affiliation: a National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry , Shanghai , People's Republic of China ;|b Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry , Shanghai , People's Republic of China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: a National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry , Shanghai , People's Republic of China ;|b Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry , Shanghai , People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Weigen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D008055:Lipids / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D053978:Pentacyclic Triterpenes / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014325:Tromethamine / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D004337:Drug Carriers; D008055:Lipids; D053978:Pentacyclic Triterpenes; D014325:Tromethamine; C017032:asiatic acid
keywords: Asiatic acid tromethamine salt; enhanced oral bioavailability; modified solvent injection; stable SLN