title: Development of a nanoparticle-based system for the delivery of retinoic acid into macrophages.
abstract: The aim of the present work is to prepare nanoparticulate systems that can target and modulate the functions of mononuclear phagocytes by local administration. All-trans retinoic acid (RA) was chosen as an immunomodulator to be encapsulated in biodegradable nanoparticles (NP). Different formulations were prepared by the nanoprecipitation method and poly(d,l)lactic acid based nanocapsules (NC) were selected to continue the study. RA-NC demonstrated a sustained release profile and an enhanced stability for 7 days. The uptake of fluorescent (NileRed) labeled NP was conducted on bone marrow derived macrophages (BMM) in vitro and xenograft glioma nude mice in vivo. Fluorescent microscopy observations and flow cytometry analysis demonstrated that NR-NC were engulfed by BMM in vitro and lasted inside over 7 days. The intratumoral injection of NR-NC confirmed that NC were efficiently uptaken by infiltrated macrophages. The effects of RA loaded NC on BMM were also evaluated by RT(2)-PCR array. Our results suggest that polymeric nanoparticles are suitable carriers to deliver RA into macrophages and can offer a new strategy in tumor macrophage-based treatment.
authors.affiliation: University Lyon, University Claude Bernard Lyon 1, Laboratoire d'Automatique et de Génie des Procédés, LAGEP UMR CNRS 5007, F-69622 Villeurbanne, France.
authors.forename: Eyad
authors.initials: E
authors.lastname: Almouazen
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bourgeois
authors.forename: Ali
authors.initials: A
authors.lastname: Boussaïd
authors.forename: Pascale
authors.initials: P
authors.lastname: Valot
authors.forename: Celine
authors.initials: C
authors.lastname: Malleval
authors.forename: Hatem
authors.initials: H
authors.lastname: Fessi
authors.forename: Serge
authors.initials: S
authors.lastname: Nataf
authors.forename: Stephanie
authors.initials: S
authors.lastname: Briançon
mesh_terms: D000818:Animals; D001692:Biological Transport; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D015552:Injections, Intralesional; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D053769:Nanocapsules; D036103:Nanotechnology; D010078:Oxazines / Q000378:metabolism; D010587:Phagocytosis; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014212:Tretinoin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D016207:Cytokines; D004337:Drug Carriers; D005456:Fluorescent Dyes; D007155:Immunologic Factors; D053769:Nanocapsules; D010078:Oxazines; D011091:Polyesters; D011108:Polymers; D012333:RNA, Messenger; C016240:polycaprolactone; D019344:Lactic Acid; C033616:poly(lactide); D014212:Tretinoin; C044808:nile red