N-acetyl-L-cysteine functionalized nanostructured lipid carrier for improving oral bioavailability of curcumin: preparation, in vitro and in vivo evaluations - PubMed (original) (raw)

N-acetyl-L-cysteine functionalized nanostructured lipid carrier for improving oral bioavailability of curcumin: preparation, in vitro and in vivo evaluations

Cihui Tian et al. Drug Deliv. 2017 Nov.

Abstract

The application of orally administered nanoparticles in the circulation system is limited by the secretion and shedding of intestinal tract mucous layer. In order to enhance mucoadhesion and mucus penetration of curcumin (Cur)-loaded nanostructured lipid carrier (NLC) after oral administration, a new multifunctional conjugate, N-acetyl-L-cysteine-polyethylene glycol (100)-monostearate (NAPG), was synthesized. Functionalized nanocarriers (Cur-NAPG-NLC) modified by different amounts of NAPG (the amounts of NAPG were 20, 50, and 100 mg) were prepared and investigated for in vitro and in vivo behavior. Mean particle sizes of 89-141 nm with negative zeta potential (-15 to -11 mV) and high encapsulation efficiency (EE, >90%) possessing spherical and stable nanocarriers were observed. Sustained drug release was also observed for the NAPG-NLC. In situ intestinal perfusion studies showed that with increasing the amount of NAPG increase absorption of Cur. In vivo oral pharmacokinetic evaluation suggested that the bioavailability of Cur in rats was proportional to the degree of functionalization of NLCs with NAPG. AUC0-t of Cur-NAPG100-NLC was improved by 499.45 and 116.89 folds as compared to that of Cur solution and unmodified Cur-NLC, respectively. In conclusion, NAPG modified NLC could be a promising drug delivery system for improving oral performance of BCS class IV drugs.

Keywords: N-acetyl-L-cysteine-polyethylene glycol (100)-monostearate; curcumin; intestinal mucus layer; nanostructure lipid carrier; oral delivery.

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Conflict of interest statement

The authors report no declarations of interest.

Figures

Figure 1.

Figure 1.

(A) Synthesis of NAPG; (B) 1H-NMR spectrum of NAC, S100, and NAPG in D2O at 25 °C; (C) schematic illustration of Cur-NAPG-NLC for oral delivery of Cur by the formation of disulfide bond between NAPG with cysteine in mucus layer and PEG coating.

Figure 2.

Figure 2.

The TEM images of (A ) Cur-NLC and (B) Cur-NAPG50-NLC; (C) Power X-ray diffraction patterns of: Cholesterol oleate (a), Cur (b), physical mixture of Cur and NAPG50-NLC (c), blank NAPG50-NLC (d) and Cur-NAPG50-NLC (e); (D) DSC curves of: Cur(a), NAPG (b), blank-NAPG50-NLC (c) and Cur-NAPG50-NLC (d).

Figure 3.

Figure 3.

In vitro cumulative drug release profiles from Cur solution, Cur-loaded NLC and NAPG-NLC in (A) pH 1.2 hydrochloric acid solution for 2 h and in pH 6.8 PBS for next 22 h and (B) physiological saline containing 1% tween 80 at 37 °C (mean ± SD; n = 3).

Figure 4.

Figure 4.

In situ single-pass perfusion, (A) Ka and (B) Peff of duodenum, jejunum and ileum. *p < .05 versus Cur solution, #p < .05 versus Cur-NLC (mean ± SD; n = 3). (C) Distribution of C6 labeled different NLC in duodenum, jejunum, and ileum after oral gavage to mice by CLSM. (D) Plasma concentration–time profiles of Cur in rats after gavage administration of Cur solution, Cur-NLC, and different Cur-NAPG-NLC at a dose of 50 mg/kg of Cur, and intravenous injection of Cur solution at a dose of 2 mg/kg of Cur. Data were presented as the mean ± SD (n = 6).

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