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Improved Oral Bioavailability and Hypolipidemic Effect of Syringic Acid via a Self-microemulsifying Drug Delivery System

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Abstract

This study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the solubility, oral bioavailability, and hypolipidemic effects of syringic acid (SA), a bioactive and poorly-soluble polyphenol. Based on the response surface methodology-central composite design (RSM-CCD), an optimum formulation of SA-SMEDDS, consisting of ethyl oleate (oil, 12.30%), Cremophor-EL (surfactant, 66.25%), 1,2-propanediol (cosurfactant, 21.44%), and drug loading (50 mg/g), was obtained. The droplets of SA-SMEDDS were nanosized (16.38 ± 0.12 nm), spherically shaped, and homogeneously distributed (PDI = 0.058 ± 0.013) nanoparticles with high encapsulation efficiency (98.04 ± 1.39%) and stability. In vitro release study demonstrated a prolonged and controlled release of SA from SMEDDS. In vitro cell studies signified that SA-SMEDDS droplets substantially promoted cellular internalization. In comparison with the SA suspension, SA-SMEDDS showed significant prolonged Tmax, t1/2, and MRT after oral administration. Also, SA-SMEDDS exhibited a delayed in vivo elimination, increased bioavailability (2.1-fold), and enhanced liver accumulation. Furthermore, SA-SMEDDS demonstrated significant improvement in alleviating serum lipid profiles and hepatic steatosis in high-fat diet-induced hyperlipidemia in mice. Collectively, SMEDDS demonstrated potential as a nanosystem for the oral delivery of SA with enhanced bioavailability and hypolipidemic effects.

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Acknowledgments

The authors thank the University Ethics Committee for the kind guidance in the animal experiments.

Funding

This work was supported by the National Natural Science Foundation of China (Grant 81720108030, 81773695, 81803475, 81373371, and 31871810), National Key Research and Development Project of China (2018YFE0208600), China Postdoctoral Science Foundation, the financial support by Key Lab for Drug Delivery & Tissue Regeneration (SS2018004), Jiangsu Provincial Research Center for Medicinal Function Development of New Food Resources, and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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  1. Congyong Sun and Wenjing Li contributed equally to this work.

Authors and Affiliations

  1. Key Lab for Drug Delivery & Tissue Regeneration, Jiangsu Provincial Research Center for Medicinal Function Development of New Food Resources, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, People’s Republic of China

    Congyong Sun, Wenjing Li, Huiyun Zhang, Michael Adu-Frimpong, Ping Ma, Yuan Zhu, Wenwen Deng, Jiangnan Yu & Ximing Xu

  2. School of Chemistry and Chemical Engineering, Yancheng Institute of Technology, Yancheng, 224003, Jiangsu, China

    Huiyun Zhang

  3. Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

    Michael Adu-Frimpong

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  1. Congyong Sun
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Sun, C., Li, W., Zhang, H. et al. Improved Oral Bioavailability and Hypolipidemic Effect of Syringic Acid via a Self-microemulsifying Drug Delivery System. AAPS PharmSciTech 22, 45 (2021). https://doi.org/10.1208/s12249-020-01901-y

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