title: Lauroyl-gemcitabine-loaded lipid nanocapsule hydrogel for the treatment of glioblastoma.
abstract: The local delivery of chemotherapeutic agents is a very promising strategy for the treatment of glioblastoma (GBM). Gemcitabine is a chemotherapeutic agent that has a different mechanism of action compared to alkylating agents and shows excellent radio-sensitizing properties. So, we developed an injectable gel-like nanodelivery system consisting in lipid nanocapsules loaded with anticancer prodrug lauroyl-gemcitabine (GemC12-LNC) in order to obtain a sustained and local delivery of this drug in the brain. In this study, the GemC12-LNC has been formulated and characterized and the viscoelastic properties of the hydrogel were evaluated after extrusion from 30G needles. This system showed a sustained and prolonged in vitro release of the drug over one month. GemC12 and the GemC12-LNC have shown increased in vitro cytotoxic activity on U-87 MG glioma cells compared to the parent hydrophilic drug. The GemC12-LNC hydrogel reduced significantly the size of a subcutaneous human GBM tumor model compared to the drug and short-term tolerability studies showed that this system is suitable for local treatment in the brain. In conclusion, this proof-of-concept study demonstrated the feasibility, safety and efficiency of the injectable GemC12-LNC hydrogel for the local treatment of GBM.
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Bastiancich
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Vanvarenberg
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Ucakar
authors.affiliation: LUNAM Université, UMR-S1066, Angers F-49933, France; INSERM U 1066, Micro et Nanomédecines Biomimétiques - MINT, Angers F-49933, France.
authors.forename: M
authors.initials: M
authors.lastname: Pitorre
authors.affiliation: LUNAM Université, UMR-S1066, Angers F-49933, France; INSERM U 1066, Micro et Nanomédecines Biomimétiques - MINT, Angers F-49933, France.
authors.forename: G
authors.initials: G
authors.lastname: Bastiat
authors.affiliation: LUNAM Université, UMR-S1066, Angers F-49933, France; INSERM U 1066, Micro et Nanomédecines Biomimétiques - MINT, Angers F-49933, France.
authors.forename: F
authors.initials: F
authors.lastname: Lagarce
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium. Electronic address: veronique.preat@uclouvain.be.
authors.forename: V
authors.initials: V
authors.lastname: Préat
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Danhier
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D065546:Drug Liberation; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D007267:Injections; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D009339:Needles; D012212:Rheology; D047368:Tumor Burden / Q000187:drug effects; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D020100:Hydrogels; D008055:Lipids; D053769:Nanocapsules; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Gemcitabine; Glioblastoma; Hydrogel; Lipid nanocapsules; Nanomedicine