title: Ameliorative Effect of Curcumin-Encapsulated Hyaluronic Acid-PLA Nanoparticles on Thioacetamide-Induced Murine Hepatic Fibrosis.
abstract: In this study, we developed curcumin-encapsulated hyaluronic acid-polylactide nanoparticles (CEHPNPs) to be used for liver fibrosis amelioration. CD44, the hyaluronic acid (HA) receptor, is upregulated on the surface of cancer cells and on activated hepatic stellate cells (aHSCs) rather than normal cells. CEHPNPs could bind to CD44 and be internalized effectively through endocytosis to release curcumin, a poor water-soluble liver protective agent. Thus, CEHPNPs were potentially not only improving drug efficiency, but also targeting aHSCs. HA and polylactide (PLA) were crosslinked by adipic acid dihydrazide (ADH). The synthesis of HA-PLA was monitored by Fourier-transform infrared (FTIR) and Nuclear Magnetic Resonance (NMR). The average particle size was approximately 60-70 nm as determined by dynamic light scattering (DLS) and scanning electron microscope (SEM). Zeta potential was around -30 mV, which suggested a good stability of the particles. This drug delivery system induced significant aHSC cell death without affecting quiescent HSCs, hepatic epithelial, and parenchymal cells. This system reduced drug dosage without sacrificing therapeutic efficacy. The cytotoxicity IC50(inhibitory concentration at 50%) value of CEHPNPs was approximately 1/30 to that of the free drug treated group in vitro. Additionally, the therapeutic effects of CEHPNPs were as effective as the group treated with the same curcumin dose intensity in vivo. CEHPNPs significantly reduced serum aspartate transaminase/alanine transaminase (ALT/AST) significantly, and attenuated tissue collagen production and cell proliferation as revealed by liver biopsy. Conclusively, the advantages of superior biosafety and satisfactory therapeutic effect mean that CEHPNPs hold great potential for treating hepatic fibrosis.
authors.affiliation: Department Applied Chemistry, College of Science and Technology, National Chi Nan University, Nantou, Puli 545, Taiwan. s99324534@ncnu.edu.tw.
authors.forename: Yu-Nong
authors.initials: YN
authors.lastname: Chen
authors.affiliation: Department Medical Education & Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan. h2326@vghtc.gov.tw.
authors.forename: Shih-Lan
authors.initials: SL
authors.lastname: Hsu
authors.affiliation: Department Chemistry, College of Sciences, National Chung Hsing University, Taichung 402, Taiwan. mliao@dragon.nchu.edu.tw.
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Liao
authors.affiliation: Department Applied Chemistry, College of Science and Technology, National Chi Nan University, Nantou, Puli 545, Taiwan. s98327510@ncnu.edu.tw.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Liu
authors.affiliation: Department Applied Chemistry, College of Science and Technology, National Chi Nan University, Nantou, Puli 545, Taiwan. a723713a@hotmail.com.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Lai
authors.affiliation: Department Applied Chemistry, College of Science and Technology, National Chi Nan University, Nantou, Puli 545, Taiwan. rosylala@gmail.com.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Chen
authors.affiliation: Department Applied Chemistry, College of Science and Technology, National Chi Nan University, Nantou, Puli 545, Taiwan. nguyenthimaihuong1989@gmail.com.
authors.forename: Mai-Huong Thi
authors.initials: MT
authors.lastname: Nguyen
authors.affiliation: Department Applied Chemistry, College of Science and Technology, National Chi Nan University, Nantou, Puli 545, Taiwan. willy51118@gmail.com.
authors.forename: Yung-Hsiang
authors.initials: YH
authors.lastname: Su
authors.affiliation: Department Applied Chemistry, College of Science and Technology, National Chi Nan University, Nantou, Puli 545, Taiwan. s104324522@mail1.ncnu.edu.tw.
authors.forename: Shang-Ting
authors.initials: ST
authors.lastname: Chen
authors.affiliation: Department Applied Chemistry, College of Science and Technology, National Chi Nan University, Nantou, Puli 545, Taiwan. lw25@ncnu.edu.tw.
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Wu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D020011:Protective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D013853:Thioacetamide
chemical_list: D018960:Hyaluronan Receptors; D011091:Polyesters; D020011:Protective Agents; D013853:Thioacetamide; C033616:poly(lactide); D006820:Hyaluronic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003474:Curcumin
keywords: curcumin; hepatic stellate cells; hyaluronic acid; liver fibrosis; nanoparticle