title: Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: a case study with the anticancer agent SNX-2112.
abstract: BACKGROUND
  SNX-2112 is a promising anticancer agent but has poor solubility in both water and oil. In the study reported here, we aimed to develop a nanocrystal formulation for SNX-2112 and to determine the pharmacokinetic behaviors of the prepared nanocrystals.
  
  
  METHODS
  Nanocrystals of SNX-2112 were prepared using the wet-media milling technique and characterized by particle size, differential scanning calorimetry, drug release, etc. Physiologically based pharmacokinetic (PBPK) modeling was undertaken to evaluate the drug's disposition in rats following administration of drug cosolvent or nanocrystals.
  
  
  RESULTS
  The optimized SNX-2112 nanocrystals (with poloxamer 188 as the stabilizer) were 203 nm in size with a zeta potential of -11.6 mV. In addition, the nanocrystals showed a comparable release profile to the control (drug cosolvent). Further, the rat PBPK model incorporating the parameters of particulate uptake (into the liver and spleen) and of in vivo drug release was well fitted to the experimental data following administration of the drug nanocrystals. The results reveal that the nanocrystals rapidly released drug molecules in vivo, accounting for their cosolvent-like pharmacokinetic behaviors. Due to particulate uptake, drug accumulation in the liver and spleen was significant at the initial time points (within 1 hour).
  
  
  CONCLUSIONS
  The nanocrystals should be a good choice for the systemic delivery of the poorly soluble drug SNX-2112. Also, our study contributes to an improved understanding of the in vivo fate of nanocrystals.
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Dong
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Huailing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Guangzhou Jinan Biomedicine Research and Development Center, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Baojian
authors.initials: B
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D013154:Spleen / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D006576:Heterocyclic Compounds, 4 or More Rings; C534922:SNX 2112
keywords: PBPK; intravenous delivery; poloxamer 188; tissue distribution
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