International Journal of Nanomedicine (Mar 2020)

Self-Microemulsifying Drug Delivery System for Improved Oral Delivery and Hypnotic Efficacy of Ferulic Acid

  • Liu CS,
  • Chen L,
  • Hu YN,
  • Dai JL,
  • Ma B,
  • Tang QF,
  • Tan XM

Journal volume & issue
Vol. Volume 15
pp. 2059 – 2070

Abstract

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Chang-Shun Liu,1– 3 Li Chen,4 Yan-Nan Hu,1– 3 Jin-Lian Dai,4 Biao Ma,4 Qing-Fa Tang,1– 3 Xiao-Mei Tan1– 3 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, People’s Republic of China; 3Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Southern Medical University, Guangzhou 510515, People’s Republic of China; 4School of Pharmacy, Zunyi Medical University, Zunyi 563000, People’s Republic of ChinaCorrespondence: Li Chen; Xiao-Mei Tan Email [email protected]; [email protected]: Ferulic acid (FA) is a natural compound which is used to treat insomnia. However, its use is limited because of its poor oral bioavailability caused by extremely rapid elimination. The current study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral delivery of FA and to enhance its hypnotic efficacy.Methods: FA-SMEDDS was prepared, and its morphology and storage stability were characterized. The formulation was also subjected to pharmacokinetic and tissue distribution studies in rats. The hypnotic efficacy of FA-SMEDDS was evaluated in p-chlorophenylalanine-induced insomnia mice.Results: FA-loaded SMEDDS exhibited a small droplet size (15.24 nm) and good stability. Oral administration of FA-SMEDDS yielded relative bioavailability of 185.96%. In the kidney, SMEDDS decreased the distribution percentage of FA from 76.1% to 59.4% and significantly reduced its metabolic conversion, indicating a reduction in renal elimination. Interestingly, FA-SMEDDS showed a higher distribution in the brain and enhanced serotonin levels in the brain, which extended the sleep time by 2-fold in insomnia mice.Conclusion: This is the first study to show that FA-loaded SMEDDS decreased renal elimination, enhanced oral bioavailability, increased brain distribution, and improved hypnotic efficacy. Thus, we have demonstrated that SMEDDS is a promising carrier which can be employed to improve the oral delivery of FA and facilitate product development for the therapy of insomnia.Keywords: insomnia, ferulic acid, oral administration, pharmacokinetics, SMEDDS

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