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Colloids Surf B Biointerfaces. 2016 Mar 1;139:52-61. doi: 10.1016/j.colsurfb.2015.11.050. Epub 2015 Nov 30.

Improved oral delivery of resveratrol from N-trimethyl chitosan-g-palmitic acid surface-modified solid lipid nanoparticles.

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College of Pharmacy, Gachon University, Incheon 406-799, South Korea. Electronic address:
College of Pharmacy, Gachon University, Incheon 406-799, South Korea. Electronic address:


Despite the therapeutic effects of resveratrol, its clinical application is restricted by its poor oral bioavailability, low water solubility, and instability. Solid lipid nanoparticles (SLNs)-based drug delivery systems have been shown to provide excellent support for the delivery of hydrophobic drugs. The poor stability and burst release behavior in stomach acidic pH conditions of SLNs result in increased aggregation of the particles in the gastrointestinal environment, limiting the success of these particles as an oral delivery system for hydrophobic drugs. N-trimethyl chitosan (TMC) graft palmitic acid (PA) (TMC-g-PA) mucoadhesive copolymer was hypothesized to be a promising candidate for the surface modification of PA-decorated resveratrol-loaded SLNs to stabilize SLNs and circumvent all the above mentioned obstacles. TMC and TMC-g-PA copolymers were therefore synthesized and characterized by (1)H-nuclear magnetic resonance ((1)H NMR) and Fourier-transformed infra-red (FT-IR) spectroscopy. Resveratrol-loaded SLNs (SLRNs) that comprised Precirol ATO 5, PA, Gelucire 50/13, Tween 80, and resveratrol as well as TMC-g-PA SLRNs were formulated and characterized in terms of physicochemical properties, stability, cytotoxicity, and in vitro and in vivo effects. The in vitro release studies of TMC-g-PA SLRNs demonstrated negligible release of resveratrol in simulated gastric and sustained release in simulated intestinal conditions and the relative bioavailability of resveratrol was furthermore found to be 3.8-fold higher from TMC-g-PA SLRNs than that from resveratrol suspension. Overall, the findings reported here indicate that TMC-g-PA SLRNs represent a potential oral drug delivery system for resveratrol.


N-trimethyl chitosan; Oral bioavailability; Palmitic acid; Resveratrol; Solid lipid nanoparticles

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