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. 2016 Sep 21:7:332.
doi: 10.3389/fphar.2016.00332. eCollection 2016.

Preparation and Characterization of Loperamide-Loaded Dynasan 114 Solid Lipid Nanoparticles for Increased Oral Absorption In the Treatment of Diarrhea

Lili Wei  1 , Yunfang Yang  2 , Kun Shi  3 , Jun Wu  4 , Wei Zhao  5 , Jingxin Mo  5
Affiliations

Preparation and Characterization of Loperamide-Loaded Dynasan 114 Solid Lipid Nanoparticles for Increased Oral Absorption In the Treatment of Diarrhea

Lili Wei et al. Front Pharmacol. .

Abstract

The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN) formulations for oral delivery of loperamide (LPM) to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114) nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a high ratio rate of lipid to drug) and LPM-SLN-2 (LPM-SLN with a low ratio rate of lipid to drug), were prepared by the solvent evaporation method. A change in the lipid concentration affects the characteristics of LPM-SLNs. The average sizes of the LPM-SLNs were 303 ± 18 nm and 519 ± 36 nm, separately, as analyzed by dynamic light scattering. The LPM-SLNs were found to be round with a smooth surface, as observed using a transmission electron microscope and a scanning electron microscope. The average encapsulation efficiencies were 87 ± 3.78% w/w and 84 ± 5.17%, accordingly. In the in vitro release experiments, LPM-SLNs showed a continuous release profile of LPM without any burst release. The oral bioavailability of LPM-SLNs was analyzed using Wistar rats. The relative bioavailabilities of LPM-SLNs were 227 and 153%, respectively, as compared that of the LPM tablet. There was no difference in the Tmax between LPM-SLN-2 and the LPM tablet. In conclusion, LPM-SLN-1 significantly improved the oral bioavailability of LPM, while LPM-SLN-2 having the same swift action as the LPM tablet. These results demonstrate the potential of LPM-SLNs in the oral delivery of LPM to treat different types of diarrhea.

Keywords: loperamide; oral delivery formulation; poorly water-soluble drugs; solid lipid nanoparticles; sustained release.

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Figures

FIGURE 1
FIGURE 1
Loperamide-loaded Dynasan 114 solid lipid nanoparticles [LPM (loperamide)-SLN (solid lipid nanoparticle)]. (A) Z-average size of LPM-SLN-1, (B) Z-average size of LPM-SLN-2, (C) SEM image of LPM-SLN-1, (D) SEM (scanning electron microscope) image of LPM-SLN-2, (E) TEM (transmission electron microscope) image of LPM-SLN-1, (F) TEM image of LPM-SLN-2; scale bar 200 nm.
FIGURE 2
FIGURE 2
(A) Typical chromatograms for loperamide HCl. (B) Calibration curve obtained for loperamide HCl in the range of 6-100 μg/ml.
FIGURE 3
FIGURE 3
Particle sizes of LPM-SLN formulations after lyophilization and reconstitution by vortexing or sonication. ∗p < 0.05.
FIGURE 4
FIGURE 4
In vitro release profile of LPM from different vehicles at (A) pH 1.2 and (B) pH 6.8. Each value represents the mean ± S.D. (n = 3).
FIGURE 5
FIGURE 5
Mean plasma LPM concentration-time curves obtained after oral administration in Wistar rats. Each value represents the mean ± S.D. (n = 6).
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