Original Article
Fenofibrate nanoliposome: Preparation and its inhibitory effects on nonalcoholic fatty liver disease in mice

https://doi.org/10.1016/j.nano.2016.07.002Get rights and content

Abstract

The aim was to prepare fenofibrate nanoliposome (FNB-Nanolipo) and investigate its characterizations, oral pharmacokinetic (PK) profiles as well as preventive and therapeutic effects on nonalcoholic fatty liver disease (NAFLD) induced by a methionine choline deficient (MCD) diet in mice. The prepared FNB-Nanolipo showed high drug loading capacity and sustained in vitro FNB release profile. Compared to FNB crude drug at equal doses, the FNB-Nanolipo given at 20 mg/kg/day (beginning on the same day when the MCD diet feeding started and lasted for 7 days) or 40 mg/kg/day (beginning after 7 days of the MCD diet feeding and lasting for another 7 days together with the MCD diet) increased plasma FNB concentration of the mice by 11.8-fold (P < 0.05) or 57.3-fold (P < 0.001), respectively, and reduced 54.7% (P < 0.05) or 35.5% (P < 0.05) of excessive hepatic lipid, respectively. The results suggest that the FNB-Nanolipo could not only significantly prevent but also efficiently treat NAFLD.

Graphical Abstract

Mice were fed with an MCD diet seven days ahead to develop NAFLD, and were then treated with saline, FNB crude drug or FNB-Nanolipo by gavage and meanwhile continuously fed with the MCD diet for another seven days. Compared to the FNB crude drug, the FNB-Nanolipo significantly enhanced oral absorption of FNB and therefore, significantly cured NAFLD induced by the MCD diet.

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Section snippets

Materials and animals

FNB was purchased from Kaifeng Pharmaceutical Co. Ltd. (Henan, China). Soybean lecithin was purchased from Tywei Pharmaceutical Co. Ltd. (Shanghai, China). Cholesterol was purchased from Damao Chemical Reagent Factory (Tianjin, China). Fenofibrate acid was purchased from J&K Scientific Ltd. (Beijing, China). HPLC-grade acetonitrile was purchased from Sigma-Aldrich (MO, USA). High-fat MCD diet was purchased from Trophic Animal Feed High-tech Co., Ltd. (Jiangsu, China).

Male C57BL/6 wild type mice

Characterizations of the FNB-Nanolipo

Data in Table 1 show that particle size of the FNB-Nanolipo determined by dynamic light scattering was 122.1 ± 1.40 nm, and polydispersity index (PDI) was 0.293, showing a uniform size distribution. Zeta potential was slightly electronegative (−2.92 mV).

Encapsulation efficacy and drug loading percentage of the FNB-Nanolipo were 96.6 ± 1.60% and 7.44 ± 4.39%, respectively.

Morphology and in vitro release of the FNB-Nanolipo

The TEM photo (Figure 1, A) shows that the FNB-Nanolipo had a spherical shape, and the particle size was between 100 and 140 nm,

Discussion

Encapsulation efficacy and drug loading percentage are important characterization parameters used to measure the ability of nanoliposomes to encapsulate drug molecules. The high encapsulation efficacy (96.6 ± 1.60%) and drug loading percentage (7.44 ± 4.39%) indicate that most of the FNB in the formulation was incorporated into the nanoliposome vesicles. The drug loading capacity was higher than some other formulations of FNB reported in the literature, including self-microemulsifying drug delivery

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    Conflict of interest: We have no conflict of interest to declare.

    1

    These two authors contribute equally to this paper.

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