title: Gastrointestinal stability, physicochemical characterization and oral bioavailability of chitosan or its derivative-modified solid lipid nanoparticles loading docetaxel.
abstract: OBJECTIVE
  The purpose of this study was to prepare the positively charged chitosan (CS)- or hydroxypropyl trimethyl ammonium chloride chitosan (HACC)-modified solid lipid nanoparticles (SLNs) loading docetaxel (DTX), and to evaluate their properties in vitro and in vivo.
  
  
  METHODS
  The DTX-loaded SLNs (DTX-SLNs) were prepared through an emulsion solvent evaporation method and further modified with CS or HACC (CS-DTX-SLNs or HACC-DTX-SLNs) via noncovalent interactions. The gastrointestinal (GI) stability, dissolution rate, physicochemical properties and cytotoxicities of SLNs were investigated. In addition, the GI mucosa irritation and oral bioavailability of SLNs were also evaluated in rats.
  
  
  RESULTS
  The HACC-DTX-SLNs were highly stable in simulated gastric and intestinal fluids (SGF and SIF). By contrast, the CS-DTX-SLNs were less stable in SIF than in SGF. The drug dissolution remarkably increased when DTX was incorporated into the SLNs, which may be attributed to the change in the crystallinity of DTX and some molecular interactions that occurred between DTX and the carriers. The SLNs showed low toxicity in Caco-2 cells and no GI mucosa irritations were observed in rats. A 2.45-fold increase in the area under the curve of DTX was found in the HACC-DTX-SLN group compared with the DTX group after the modified SLNs were orally administered to rats. However, the oral absorption of DTX-SLN or CS-DTX-SLN group showed no significant difference compared with that of DTX group.
  
  
  CONCLUSIONS
  The positively charged HACC-DTX-SLNs with a stable particle size could provide the enhanced oral bioavailability of DTX in rats.
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China.|b College of Medicine, Jiaxing University , Jiaxing , People's Republic of China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Shi
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China.
authors.forename: Jiang-Yan
authors.initials: JY
authors.lastname: Liu
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China.
authors.forename: Xiao-Xue
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Zhang
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China.
authors.forename: Jing-Hao
authors.initials: JH
authors.lastname: Cui
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China.
authors.forename: Qing-Ri
authors.initials: QR
authors.lastname: Cao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001826:Body Fluids / Q000378:metabolism; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism*; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation / Q000187:drug effects; D004655:Emulsions / Q000737:chemistry / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D043823:Taxoids / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D043823:Taxoids; D000077143:Docetaxel; D048271:Chitosan
keywords: Docetaxel; chitosan; oral bioavailability; solid lipid nanoparticles; stability