Improving the ameliorative effects of berberine and curcumin combination via dextran-coated bilosomes on non-alcohol fatty liver disease in mice

Journal of Nanobiotechnology

Zhaohui Jiang¹  Jiyuan Zhang²  Qianming Du³  Jinzhuan Xu⁴  Jia Zhou⁴  Runbin Sun⁵  Jing Huang⁶  Zipeng Gong⁶  Yuan Lu⁶  Jianqing Peng⁷  Xiangchun Shen⁷  Yi Chen⁷ 

[1] Department of Clinical Laboratory, The First People’s Hospital of Guiyang, 550002, Guiyang, China;Department of Clinical Pharmacy, School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, 210009, Nanjing, China;General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China;Department of Clinical Pharmacy, School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, 210009, Nanjing, China;Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, 550025, Guiyang, China;Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, China;State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014, Guiyang, China;State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014, Guiyang, China;Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, 550025, Guiyang, China;

关键词: Berberine;    Curcumin;    Bilosomes;    DEAE-DEX;    Oral delivery;    NAFLD;   

DOI  :  10.1186/s12951-021-00979-1

来源: Springer

【 摘 要 】

BackgroundThe combination of berberine (BER) and curcumin (CUR) has been verified with ameliorative effects on non-alcohol fatty liver disease (NAFLD). However, discrepant bioavailability and biodistribution of BER and CUR remained an obstacle to achieve synergistic effects. Multilayer nanovesicles have great potential for the protection and oral delivery of drug combinations. Therein lies bile salts inserted liposomes, named as bilosomes, that possesses long residence time in the gastrointestinal tract (GIT) and permeability across the small intestine. Diethylaminoethyl dextran (DEAE-DEX) is generally used as an outside layer on the nanovesicles to increase the mucinous stability and promote oral absorption. Herein, we developed a DEAE-DEX-coated bilosome with BER and CUR encapsulated (DEAE-DEX@LSDBC) for the treatment of NAFLD.ResultsDEAE-DEX@LSDBC with 150 nm size exhibited enhanced permeation across mucus and Caco-2 monolayer. In vivo pharmacokinetics study demonstrated that DEAE-DEX@LSDBC profoundly prolonged the circulation time and improved the oral absorption of both BER and CUR. Intriguingly, synchronized biodistribution of BER and CUR and highest biodistribution at liver was achieved by DEAE-DEX@LSDBC, which contributed to the optimal ameliorative effects on NAFLD. It was further verified to be mainly mediated by anti-oxidation and anti-inflammation related pathwaysConclusionDEAE-DEX coated bilosome displayed promoted oral absorption, prolonged circulation and synchronized biodistribution of BER and CUR, leading to improved ameliorative effects on NAFLD in mice, which provided a promising strategy for oral administration of drug combinations.Graphic abstract

【 授权许可】

CC BY