title: Hyaluronic acid-coated, prodrug-based nanostructured lipid carriers for enhanced pancreatic cancer therapy.
abstract: BACKGROUND
  Gemcitabine (GEM) and Baicalein (BCL) are reported to have anti-tumor effects including pancreatic cancer. Hyaluronic acid (HA) can bind to over-expressed receptors in various kinds of cancer cells.
  
  
  OBJECTIVE
  The aim of this study is to develop prodrugs containing HA, BCL and GEM, and construct nanomedicine incorporate GEM and BCL in the core and HA on the surface. This system could target the cancer cells and co-deliver the drugs.
  
  
  METHODS
  GEM-stearic acid lipid prodrug (GEM-SA) and hyaluronic acid-amino acid-baicalein prodrug (HA-AA-BCL) were synthesized. Then, GEM and BCL prodrug-based targeted nanostructured lipid carriers (HA-GEM-BCL NLCs) were prepared by the nanoprecipitation technique. The in vitro cytotoxicity studies of the NLCs were evaluated on AsPC1 pancreatic cancer cell line. In vivo anti-tumor effects were observed on the murine-bearing pancreatic cancer model.
  
  
  RESULTS
  HA-GEM-BCL NLCs were effective in entering pancreatic cancer cells over-expressing HA receptors, and showed cytotoxicity of tumor cells in vitro. In vivo study revealed significant tumor growth inhibition ability of HA-GEM-BCL NLCs in murine pancreatic cancer model.
  
  
  CONCLUSIONS
  It could be concluded that HA-GEM-BCL NLCs could be featured as promising co-delivery, tumor-targeted nanomedicine for the treatment of cancers.
authors.affiliation: a Department of Pharmacy , Linyi People's Hospital , Linyi , Shandong , China.
authors.forename: Zhihe
authors.initials: Z
authors.lastname: Lu
authors.affiliation: b Department of Science and Education , Linyi People's Hospital , Linyi , Shandong , China.
authors.forename: Jingrong
authors.initials: J
authors.lastname: Su
authors.affiliation: a Department of Pharmacy , Linyi People's Hospital , Linyi , Shandong , China.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Li
authors.affiliation: c Department of Pediatric Nephrologist , Linyi People's Hospital , Linyi , Shandong , China.
authors.forename: Yuzhu
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: d Department of Neurology , Linyi People's Hospital , Linyi , Shandong , China.
authors.forename: Decai
authors.initials: D
authors.lastname: Ye
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D044950:Flavanones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D047368:Tumor Burden / Q000187:drug effects / Q000502:physiology; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D044950:Flavanones; D008055:Lipids; D011355:Prodrugs; D003841:Deoxycytidine; C006680:baicalein; D006820:Hyaluronic Acid; D000093542:Gemcitabine
keywords: Pancreatic cancer; hyaluronic acid; lipid prodrug; nanostructured lipid carriers; synergistic combination therapy