title: Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin.
abstract: OBJECTIVE
  The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin.
  
  
  METHODS
  The formulation was optimized by Plackett-Burman screening design and Box-Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin.
  
  
  RESULTS
  The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of -24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t(1/2) of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p < 0.01). The in situ intestinal absorption study revealed that the effective permeability (Peff) value of curcumin for SLNs was significantly improved (p < 0.01) comparing to curcumin solution.
  
  
  CONCLUSIONS
  Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.
authors.affiliation: a Department of Pharmacy, the Second Affiliated Hospital, Harbin Medical University , Key Laboratory of Medications Research, College of Heilongjiang Province , Harbin , P. R. China and.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Ji
authors.affiliation: b Department of Pharmaceutics, School of Pharmacy , Harbin Medical University , Harbin , P. R. China.
authors.forename: Jingling
authors.initials: J
authors.lastname: Tang
authors.affiliation: a Department of Pharmacy, the Second Affiliated Hospital, Harbin Medical University , Key Laboratory of Medications Research, College of Heilongjiang Province , Harbin , P. R. China and.|b Department of Pharmaceutics, School of Pharmacy , Harbin Medical University , Harbin , P. R. China.
authors.forename: Mengting
authors.initials: M
authors.lastname: Li
authors.affiliation: a Department of Pharmacy, the Second Affiliated Hospital, Harbin Medical University , Key Laboratory of Medications Research, College of Heilongjiang Province , Harbin , P. R. China and.|b Department of Pharmaceutics, School of Pharmacy , Harbin Medical University , Harbin , P. R. China.
authors.forename: Jinmei
authors.initials: J
authors.lastname: Ren
authors.affiliation: a Department of Pharmacy, the Second Affiliated Hospital, Harbin Medical University , Key Laboratory of Medications Research, College of Heilongjiang Province , Harbin , P. R. China and.|b Department of Pharmaceutics, School of Pharmacy , Harbin Medical University , Harbin , P. R. China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zheng
authors.affiliation: a Department of Pharmacy, the Second Affiliated Hospital, Harbin Medical University , Key Laboratory of Medications Research, College of Heilongjiang Province , Harbin , P. R. China and.|b Department of Pharmaceutics, School of Pharmacy , Harbin Medical University , Harbin , P. R. China.
authors.forename: Linhua
authors.initials: L
authors.lastname: Wu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004339:Drug Compounding; D006207:Half-Life; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008657:Metabolic Clearance Rate; D008956:Models, Chemical; D015233:Models, Statistical; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D017208:Rats, Wistar; D012995:Solubility; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014810:Vitamin E / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004337:Drug Carriers; D008055:Lipids; D013501:Surface-Active Agents; D014810:Vitamin E; D011092:Polyethylene Glycols; C043444:octadecyl polyoxyethylene ether; D003474:Curcumin; C014225:tocophersolan
keywords: Curcumin; P-glycoprotein; in situ intestinal absorption; oral bioavailability; solid lipid nanoparticles