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Qin Yang,1,2,* Tiantian Tan,2,* Qin He,2 Chenqi Guo,2 Dan Chen,2 Yulu Tan,2 Jiaxing Feng,2 Xu Song,2 Tao Gong,2 Jia Li3 1School of Pharmacy, North Sichuan Medical College, Nanchong 637100, People’s Republic of China; 2Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People’s Republic of China; 3West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia Li, West China Hospital of Stomatology, Sichuan University, No. 14, Block 3, Southern Renmin Road, Chengdu, 610041, People’s Republic of China, Tel +862885503503, Email lijia816@163.comIntroduction: Silybin (SLB) as an effective hepatoprotective phytomedicine has been limited by its hydrophobicity, poor bioavailability and accumulation at lesion sites. Additionally, present drug loading methods are impeded by their low drug loading capacity, potential hazard of materials and poor therapeutic effects. Consequently, there is a pressing need to devise an innovative approach for preparing nanosuspensions loaded with both SLB and Silybin Meglumine salt (SLB-M), as well as to investigate the therapeutic effects of SLB nanosuspensions against hepatic fibrosis.Methods: The SLB nanosuspension (NS-SLB) was prepared and further modified with a hyaluronic acid–cholesterol conjugate (NS-SLB-HC) to improve the CD44 targeting proficiency of NS-SLB. To validate the accumulation of CD44 and ensure minimal cytotoxicity, cellular uptake and cytotoxicity assessments were carried out for the nanosuspensions. Western blotting was employed to evaluate the anti-hepatic fibrosis efficacy in LX-2 cells by inhibiting the secretion of collagen I. Hepatic fibrosis mouse models were used to further confirm the effectiveness of NS-SLB and NS-SLB-HC against hepatic fibrosis in vivo.Results: Uniform nanosuspensions were prepared through self-assembly, achieving high drug loading rates of 89.44% and 60.67%, respectively. Both SLB nanosuspensions showed minimal cytotoxicity in cellular environments and mitigated hepatic fibrosis in vitro. NS-SLB-HC was demonstrated to target activated hepatic stellate cells by receptor-ligand interaction between HA and CD44. They can reverse hepatic fibrosis in vivo by downregulating TGF-β and inhibiting the secretion of α-SMA and collagen I.Conclusion: Designed as a medical excipient analogue, SLB-M was aimed to establish an innovative nanosuspension preparation method, characterized by high drug loading capacity and a notable impact against hepatic fibrosis.Keywords: nanosuspension, LX-2 cells, phytomedicines, surfactant, drug delivery system |
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