title: Enhanced oral delivery of curcumin from N-trimethyl chitosan surface-modified solid lipid nanoparticles: pharmacokinetic and brain distribution evaluations.
abstract: OBJECTIVE
  Solid lipid nanoparticles (SLNs) have been proposed as a colloidal carrier system that could enhance the oral bioavailability of curcumin. However, a burst release of the loaded drug, which occurs in acidic environments, has been a main obstacle to the oral delivery of curcumin by using SLNs as a carrier system. We hypothesized that a quarternized chitosan derivative could be used for acid-resistant coating to stabilize the SLNs and circumvent the burst release.
  
  
  METHODS
  N-trimethyl chitosan (TMC) was synthesized and determined by (1)H-NMR and FT-IR. To investigate the details of chitosan and TMC surface modification on SLCNs composed of palmitic acid, cholesterol, TPGS and curcumin, a number of factors such as optimized SLNs composition, solid state characterization, stability, cell viability, in vitro release in GI conditions, curcumin oral bioavailability and brain distribution studies, were evaluated.
  
  
  RESULTS
  The TMC-SLCNs exhibited prolonged stability in room and refrigerated conditions, controlled drug release in simulated intestinal fluid, significantly higher oral bioavailability, and brain distribution of curcumin than free curcumin, chitosan and non-coated SLCNs.
  
  
  CONCLUSIONS
  These finding suggests that the TMC-SLCNs is a promising nanocarrier system for oral delivery and brain distribution of curcumin.
authors.affiliation: College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon, 406-799, South Korea.
authors.forename: Prakash
authors.initials: P
authors.lastname: Ramalingam
authors.forename: Young Tag
authors.initials: YT
authors.lastname: Ko
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D048271:Chitosan / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D061986:MCF-7 Cells; D008297:Male; D008546:Melanoma, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D011897:Random Allocation; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D004337:Drug Carriers; D008055:Lipids; C118071:N-trimethyl chitosan chloride; D048271:Chitosan
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