title: Self-assembled biotransesterified cyclodextrins as potential Artemisinin nanocarriers. II: In vitro behavior toward the immune system and in vivo biodistribution assessment of unloaded nanoparticles.
abstract: In a previous study, we reported on the formulation of Artemisinin-loaded surface-decorated nanoparticles (nanospheres and nanoreservoirs) by co-nanoprecipitation of PEG derivatives (PEG1500 and PEG4000-stearate, polysorbate 80) and biosynthesized γ-CD fatty esters. In the present study, the co-nanoprecipitation was extended to the use of a PEGylated phospholipid, namely DMPE-PEG2000. As our goal was to prepare long-circulating nanocarriers for further systemic delivery of Artemisinin (ART), here, we have investigated, on the one hand, the in vitro behavior of these surface-modified γ-CD-C10 particles toward the immune system (complement activation and macrophage uptake assays) and, on the other hand, their biodistribution features in mice. These experiments showed that the in vitro plasma protein adsorption and phagocytosis by macrophage cells triggered by γ-CD-C10 nanoparticles were significantly reduced when their surface was decorated with amphiphilic PEGylated molecules, in particular PEG1500-stearate, DMPE-mPEG2000 or polysorbate 80. The prolonged blood circulation time assessed by fluorescence imaging was demonstrated for unloaded γ-CD-C10-based nanospheres and nanoreservoir particles containing DMPE-PEG2000 and polysorbate80, respectively. These nanoparticles also proved to be non-hemolytic at the concentration range used in vivo. Within the limits of the conducted experiments, the co-nanoprecipitation technique may be considered as an alternative for surface modification of amphiphilic CD-based drug delivery systems and may be applied to the systemic delivery of ART.
authors.affiliation: DPM, UMR CNRS 5063, ICMG FR 2607, University of Grenoble, France; UFR/SDS, University of Ouagadougou, Burkina Faso.
authors.forename: Josias B G
authors.initials: JB
authors.lastname: Yaméogo
authors.affiliation: DPM, UMR CNRS 5063, ICMG FR 2607, University of Grenoble, France. Electronic address: annabelle.geze@ujf-grenoble.fr.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Gèze
authors.affiliation: DPM, UMR CNRS 5063, ICMG FR 2607, University of Grenoble, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Choisnard
authors.affiliation: CERMAV, UPR CNRS 5301, ICMG FR 2607, BP 53, Grenoble Cedex 9, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Putaux
authors.affiliation: DPM, UMR CNRS 5063, ICMG FR 2607, University of Grenoble, France.
authors.forename: Roseline
authors.initials: R
authors.lastname: Mazet
authors.affiliation: INSERM U1066, Micro et Nanomédecines Biomimétiques, IBS-CHU, Angers, University of Angers, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Passirani
authors.affiliation: INSERM U823, Grenoble, France; Université Joseph Fourier, Grenoble, France.
authors.forename: Michelle
authors.initials: M
authors.lastname: Keramidas
authors.affiliation: INSERM U823, Grenoble, France; Université Joseph Fourier, Grenoble, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Coll
authors.affiliation: INSERM U1066, Micro et Nanomédecines Biomimétiques, IBS-CHU, Angers, University of Angers, France.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Lautram
authors.affiliation: INSERM U1066, Micro et Nanomédecines Biomimétiques, IBS-CHU, Angers, University of Angers, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bejaud
authors.affiliation: UFR/SDS, University of Ouagadougou, Burkina Faso.
authors.forename: Rasmané
authors.initials: R
authors.lastname: Semdé
authors.affiliation: DPM, UMR CNRS 5063, ICMG FR 2607, University of Grenoble, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Wouessidjewe
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D037621:Artemisinins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D002460:Cell Line; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D012756:Sheep; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000890:Anti-Infective Agents; D037621:Artemisinins; D003505:Cyclodextrins; D004337:Drug Carriers; C031327:artemisinin
keywords: Artemisinin; Biodistribution; Bioesterified γ-cyclodextrins; Co-nanoprecipitation; Hemolytic properties; PEGylated amphiphiles; Stealth properties; Surface-decorated nanoparticles