Enhanced Oral Delivery of Curcumin from N-trimethyl Chitosan Surface-Modified Solid Lipid Nanoparticles: Pharmacokinetic and Brain Distribution Evaluations
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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.
N-trimethyl chitosan (TMC) was synthesized and determined by 1H-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.
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.
These finding suggests that the TMC-SLCNs is a promising nanocarrier system for oral delivery and brain distribution of curcumin.
Key wordscoating curcumin N-trimethyl chitosan oral drug delivery solid lipid nanoparticles
Chitosan coated solid lipid nanoparticles
Differential scanning calorimetry
Fourier transform-infrared spectroscopy
Proton nuclear magnetic resonance spectroscopy
High performance liquid chromatography
Liquid chromatography – tandem mass spectroscopy
- MTT reagent
(3-[4, 5-dimethyl –thiazol-2-yl]-2, 5-diphenyl tetrazolium bromide)
Powder X-ray diffraction
Curcumin-loaded solid lipid nanoparticles
Solid lipid nanoparticles
N-trimethyl chitosan coated solid lipid nanoparticles
d-α-tocopheryl polyethylene glycol 1,000 succinate
This research was supported by the Basic Science Research Program of Korean National Research Foundation (NRF-20110007794).
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