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Enhanced Oral Delivery of Curcumin from N-trimethyl Chitosan Surface-Modified Solid Lipid Nanoparticles: Pharmacokinetic and Brain Distribution Evaluations

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ABSTRACT

Purpose

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 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.

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.

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Abbreviations

CH-SLCNs:

Chitosan coated solid lipid nanoparticles

DSC:

Differential scanning calorimetry

FT-IR:

Fourier transform-infrared spectroscopy

H-NMR:

Proton nuclear magnetic resonance spectroscopy

HPLC:

High performance liquid chromatography

LC-MS/MS:

Liquid chromatography – tandem mass spectroscopy

MTT reagent:

(3-[4, 5-dimethyl –thiazol-2-yl]-2, 5-diphenyl tetrazolium bromide)

PXRD:

Powder X-ray diffraction

SLCNs:

Curcumin-loaded solid lipid nanoparticles

SLNs:

Solid lipid nanoparticles

TGA:

Thermogravimetric analysis

TMC:

N-trimethyl chitosan

TMC-SLCNs:

N-trimethyl chitosan coated solid lipid nanoparticles

TPGS:

d-α-tocopheryl polyethylene glycol 1,000 succinate

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Acknowledgments

This research was supported by the Basic Science Research Program of Korean National Research Foundation (NRF-20110007794).

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Authors and Affiliations

  1. College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon, 406-799, South Korea

    Prakash Ramalingam & Young Tag Ko

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  1. Prakash Ramalingam
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  2. Young Tag Ko
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Correspondence to Young Tag Ko.

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Ramalingam, P., Ko, Y.T. Enhanced Oral Delivery of Curcumin from N-trimethyl Chitosan Surface-Modified Solid Lipid Nanoparticles: Pharmacokinetic and Brain Distribution Evaluations. Pharm Res 32, 389–402 (2015). https://doi.org/10.1007/s11095-014-1469-1

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  • DOI: https://doi.org/10.1007/s11095-014-1469-1

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