Preparation and characterization of fenofibrate-loaded nanostructured lipid carriers for oral bioavailability enhancement.

Tuan Hiep Tran,Jong Oh Kim,Thiruganesh Ramasamy,Han-Gon Choi,Chul Soon Yong,Duy Hieu Truong

doi:10.1208/s12249-014-0175-y

Tuan Hiep Tran, Jong Oh Kim + Show 4 more

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https://doi.org/10.1208/s12249-014-0175-y

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Journal: AAPS PharmSciTech	Publication Date: Jul 18, 2014
Citations: 114	License type: cc-by

Affiliation: Yeungnam University, Hanyang University

Abstract

The aim of this study is to investigate the potential of nanostructured lipid carriers (NLCs) in improving the oral bioavailability of a lipid lowering agent, fenofibrate (FEN). FEN-loaded NLCs (FEN-NLCs) were prepared by hot homogenization followed by an ultrasonication method using Compritol 888 ATO as a solid lipid, Labrafil M 1944CS as a liquid lipid, and soya lecithin and Tween 80 as emulsifiers. NLCs were characterized in terms of particle size and zeta potential, surface morphology, encapsulation efficiency, and physical state properties. Bioavailability studies were carried out in rats by oral administration of FEN-NLC. NLCs exhibited a spherical shape with a small particle size (84.9 ± 4.9 nm). The drug entrapment efficiency was 99% with a loading capacity of 9.93 ± 0.01% (w/w). Biphasic drug release manner with a burst release initially, followed by prolonged release was depicted for in vitro drug release studies. After oral administration of the FEN-NLC, drug concentration in plasma and AUCt-∞ was fourfold higher, respectively, compared to the free FEN suspension. According to these results, FEN-NLC could be a potential delivery system for improvement of loading capacity and control of drug release, thus prolonging drug action time in the body and enhancing the bioavailability.

Highlights

Fenofibrate (FEN), a isopropyl ester of 2-(4-[4-chlorobenzoyl] phenoxy)-2-methylpropanoic acid been used regularly to reduce elevated levels of cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, total triglycerides, and triglyceride-rich very low-density lipoprotein [1,2]
Nanoparticle size was increased with the increasing amount of Labrafil, followed by a decrease in size when the proportion of liquid lipid exceeded 10% w/w
Trends similar to those of blank NP were observed for FEN-nanostructured lipid carriers (NLCs), and addition of FEN had a negligible effect on the size and polydispersity index (PDI) of blank NP

Summary

Introduction

Fenofibrate (FEN), a isopropyl ester of 2-(4-[4-chlorobenzoyl] phenoxy)-2-methylpropanoic acid been used regularly to reduce elevated levels of cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, total triglycerides, and triglyceride-rich very low-density lipoprotein [1,2] It is used alone or in combination with statins in treatment of hypercholesterolemia and hypertriglyceridemia. Despite of several above advantages, SLNs have to face some challenger such as relatively low drug loading capacity, associating with gelation, drug leakage, and possible expulsion of the drug during storage [11] These problems were resolved with introduction of nanostructured lipid carriers (NLCs), a second generation of SLNs. NLCs have a solid matrix blended with a liquid lipid (oil) to form an unstructured matrix that improved the drug loading capacity of nanoparticles and reduced drug expulsion from the matrix during storage [12,13]. Passage of NLCs through multiple biological barriers and efficient transport the therapeutic moiety via the lymphatic pathway for enhancement of the oral bioavailability has been demonstrated [14]

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