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 pote\ntial, 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.
References
Lee DW, Marasini N, Poudel BK, Kim JH, Cho HJ, Moon BK, et al. Application of Box-Behnken design in the preparation and optimization of fenofibrate-loaded self-microemulsifying drug delivery system (SMEDDS). J Microencapsul. 2014;31(1):31–40.
Zuo B, Sun Y, Li H, Liu X, Zhai Y, Sun J, et al. Preparation and in vitro/in vivo evaluation of fenofibrate nanocrystals. Int J Pharm. 2013;455(1):267–75.
Niu X, Wan L, Hou Z, Wang T, Sun C, Sun J, et al. Mesoporous carbon as a novel drug carrier of Fenofibrate for enhancement of the dissolution and oral bioavailability. Int J Pharm. 2013;452(1–2):382–9.
Kim GG, Poudel BK, Marasini N, Lee DW, Hiep TT, Yang KY, et al. Enhancement of oral bioavailability of fenofibrate by solid self-microemulsifying drug delivery systems. Drug Dev Ind Pharm. 2013;39(9):1431–8.
Li X, Gu L, Xu Y, Wang Y. Preparation of fenofibrate nanosuspension and study of its pharmacokinetic behavior in rats. Drug Dev Ind Pharm. 2009;35(7):827–33.
Hanafy A, Spahn-Langguth H, Vergnault G, Grenier P, Tubic Grozdanis M, Lenhardt T, et al. Pharmacokinetic evaluation of oral fenofibrate nanosuspensions and SLN in comparison to conventional suspensions of micronized drug. Adv Drug Deliv Rev. 2007;59(6):419–26.
He H, Yang R, Tang X. in vitro and in vivo evaluation of fenofibrate solid dispersion prepared by hot-melt extrusion. Drug Dev Ind Pharm. 2010;36(6):681–7.
Tran TH, Ramasamy T, Cho HJ, Kim YI, Poudel BK, Choi HG, et al. Formulation and optimization of raloxifene-loaded solid lipid nanoparticles to enhance oral bioavailability. J Nanosci Nanotechnol. 2014;14(7):4820–31.
Ramasamy T, Khandasami US, Ruttala H, Shanmugam S. Development of solid lipid nanoparticles enriched hydrogels for topical delivery of anti-fungal agent. Macromol Res. 2012;20(7):682–92.
Subedi RK, Kang KW, Choi H-K. Preparation and characterization of solid lipid nanoparticles loaded with doxorubicin. Eur J Pharm Sci. 2009;37(3):508–13.
Ramasamy T, Tran TH, Choi JY, Cho HJ, Kim JH, Choi HG, et al. Layer-by-layer coated lipid-polymer hybrid nanoparticles designed for use in anticancer drug delivery. Carbohydr Polym. 2014;102:653–61.
Beloqui A, Solinís MÁ, Gascón AR, del Pozo-Rodríguez A, des Rieux A, Préat V. Mechanism of transport of saquinavir-loaded nanostructured lipid carriers across the intestinal barrier. J Control Release. 2013;166(2):115–23.
Zhuang C-Y, Li N, Wang M, Zhang X-N, Pan W-S, Peng J-J, et al. Preparation and characterization of vinpocetine loaded nanostructured lipid carriers (NLC) for improved oral bioavailability. Int J Pharm. 2010;394(1):179–85.
Khan AA, Mudassir J, Mohtar N, Darwis Y. Advanced drug delivery to the lymphatic system: lipid-based nanoformulations. Int J Nanomedicine. 2013;8:2733–44.
Agrawal Y, Petkar KC, Sawant KK. Development, evaluation and clinical studies of Acitretin loaded nanostructured lipid carriers for topical treatment of psoriasis. Int J Pharm. 2010;401(1):93–102.
Hu F-Q, Jiang S-P, Du Y-Z, Yuan H, Ye Y-Q, Zeng S. Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Colloids Surf B: Biointerfaces. 2005;45(3):167–73.
Aji Alex M, Chacko A, Jose S, Souto E. Lopinavir loaded solid lipid nanoparticles (SLN) for intestinal lymphatic targeting. Eur J Pharm Sci. 2011;42(1):11–8.
Lin X, Li X, Zheng L, Yu L, Zhang Q, Liu W. Preparation and characterization of monocaprate nanostructured lipid carriers. Colloids Surf A Physicochem Eng Asp. 2007;311(1):106–11.
Ige PP, Baria RK, Gattani SG. Fabrication of fenofibrate nanocrystals by probe sonication method for enhancement of dissolution rate and oral bioavailability. Colloids Surf B: Biointerfaces. 2013;108:366–73.
Huang X, Chen Y-J, Peng D-Y, Li Q-L, Wang X-S, Wang D-L, et al. Solid lipid nanoparticles as delivery systems for Gambogenic acid. Colloids Surf B: Biointerfaces. 2013;102:391–7.
Abdelbary G, Fahmy RH. Diazepam-loaded solid lipid nanoparticles: design and characterization. AAPS PharmSciTech. 2009;10(1):211–9.
Patel AR, Vavia PR. Preparation and in vivo evaluation of SMEDDS (Self-microemulsifying drug delivery system) containing fenofibrate. AAPS J. 2007;9(3):E344–52.
Hussain N, Jaitley V, Florence AT. Recent advances in the understanding of uptake of microparticulates across the gastrointestinal lymphatics. Adv Drug Deliv Rev. 2001;50(1):107–42.
Vasir JK, Tambwekar K, Garg S. Bioadhesive microspheres as a controlled drug delivery system. Int J Pharm. 2003;255(1):13–32.
Luo Y, Chen D, Ren L, Zhao X, Qin J. Solid lipid nanoparticles for enhancing vinpocetine’s oral bioavailability. J Control Release. 2006;114(1):53–9.
Zhang T, Chen J, Zhang Y, Shen Q, Pan W. Characterization and evaluation of nanostructured lipid carrier as a vehicle for oral delivery of etoposide. Eur J Pharm Sci. 2011;43(3):174–9.
Kumar VV, Chandrasekar D, Ramakrishna S, Kishan V, Rao YM, Diwan PV. Development and evaluation of nitrendipine loaded solid lipid nanoparticles: influence of wax and glyceride lipids on plasma pharmacokinetics. Int J Pharm. 2007;335(1):167–75.
Acknowledgments
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (No. 2012R1A2A2A02044997 and No. 2012R1A1A1039059).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Tran, T.H., Ramasamy, T., Truong, D.H. et al. Preparation and Characterization of Fenofibrate-Loaded Nanostructured Lipid Carriers for Oral Bioavailability Enhancement. AAPS PharmSciTech 15, 1509–1515 (2014). https://doi.org/10.1208/s12249-014-0175-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-014-0175-y