title: Safe lipid nanocapsule-based gel technology to target lymph nodes and combat mediastinal metastases from an orthotopic non-small-cell lung cancer model in SCID-CB17 mice.
abstract: The purpose of this study is the assessment of gel technology based on a lauroyl derivative of gemcitabine encapsulated in lipid nanocapsules delivered subcutaneously or intravenously after dilution to (i) target lymph nodes, (ii) induce less systemic toxicity and (iii) combat mediastinal metastases from an orthotopic model of human, squamous, non-small-cell lung cancer Ma44-3 cells implanted in severe combined immunodeficiency mice. The gel technology mainly targeted lymph nodes as revealed by the biodistribution study. Moreover, the gel technology induced no significant myelosuppression (platelet count) in comparison with the control saline group, unlike the conventional intravenous gemcitabine hydrochloride treated group (P<0.05). Besides, the gel technology, delivered subcutaneously twice a week, was able to combat locally mediastinal metastases from the orthotopic lung tumor and to significantly delay death (P<0.05) as was the diluted gel technology delivered intravenously three times a week.
  
  
  BACKGROUND
  Lung cancer is one of the leading causes of mortality worldwide. A significant proportion of patients with this disease have lymph node metastasis. In this study, the authors investigated the use of lipid nanocapsules, loaded with the lipophilic pro-drug gemcitabine for targeting tumors in lymph nodes after subcutaneous injection. This delivery method was shown to be effective in controlling tumor progression and may be useful in future clinical use.
authors: LUNAM Université - Micro et Nanomédecines Biomimétiques, Angers, France; INSERM - U1066 IBS-CHU, Angers, France. Electronic address: nathalie.wauthoz@univ-angers.fr.
authors: Nathalie
authors: N
authors: Wauthoz
authors: LUNAM Université - Micro et Nanomédecines Biomimétiques, Angers, France; INSERM - U1066 IBS-CHU, Angers, France. Electronic address: guillaume.bastiat@univ-angers.fr.
authors: Guillaume
authors: G
authors: Bastiat
authors: LUNAM Université - Micro et Nanomédecines Biomimétiques, Angers, France; INSERM - U1066 IBS-CHU, Angers, France. Electronic address: elodie.moysan@etud.univ-angers.fr.
authors: Elodie
authors: E
authors: Moysan
authors: LUNAM Université - Micro et Nanomédecines Biomimétiques, Angers, France; INSERM - U1066 IBS-CHU, Angers, France. Electronic address: anna.cieslak@etud.univ-angers.fr.
authors: Anna
authors: A
authors: Cieślak
authors: Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. Electronic address: kondo@clin.med.tokushima-u.ac.jp.
authors: Kazuya
authors: K
authors: Kondo
authors: Hematology Department, Academic Hospital, Angers, France. Electronic address: MaZandecki@chu-angers.fr.
authors: Marc
authors: M
authors: Zandecki
authors: Biochemistry Department, Academic Hospital, Angers, France. Electronic address: VaMoal@chu-angers.fr.
authors: Valérie
authors: V
authors: Moal
authors: Cell and Tissue Pathology Department, Academic Hospital, Angers, France. Electronic address: MCRousselet@chu-angers.fr.
authors: Marie-Christine
authors: MC
authors: Rousselet
authors: LUNAM Université - Micro et Nanomédecines Biomimétiques, Angers, France; Pneumology Department, Academic Hospital, Angers, France. Electronic address: johureaux@chu-angers.fr.
authors: José
authors: J
authors: Hureaux
authors: LUNAM Université - Micro et Nanomédecines Biomimétiques, Angers, France; INSERM - U1066 IBS-CHU, Angers, France. Electronic address: jean-pierre.benoit@univ-angers.fr.
authors: Jean-Pierre
authors: JP
authors: Benoit
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology / Q000517:prevention & control*; D008482:Mediastinum / Q000473:pathology; D008819:Mice, Nude; D016513:Mice, SCID; D053769:Nanocapsules / Q000737:chemistry*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D008055:Lipids; D053769:Nanocapsules; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Immunomodulation; Lymphatic targeting; Mediastinum; Nanomedicine