title: Functionalizing Nanoemulsions with Carboxylates: Impact on the Biodistribution and Pharmacokinetics in Mice.
abstract: Efficiency of drug administration is related to the inhibition of adverse effects, and can be improved by drug targeting through lipid nanocarriers encapsulation. Targeting technology generally goes along with the nanocarrier functionalization that can be surface modification and/or ligand grafting. The great advantage of nanoemulsions is their loading capability and the possibilities to encapsulate several entities in a single droplet, however, the decoration of the lipid droplets with strongly anchored reactive functions is challenging. This study proposes a reliable and innovative method to functionalize lipid droplets, based on the lipophilic polymer poly(maleic anhydride-alt-1-octadecene), solubilized in the droplet core, and able to hydrolyze at the oil/water interface. Interfacial chemistry and physicochemical properties of nanodroplets are characterized. In vitro studies reveal that the presence of carboxylates at interface has a strong impact on the interactions with cells, as the internalization of functionalized droplets is much higher than control ones. This difference is confirmed with longitudinal computed tomography studies in mice after i.v. administration, strongly impacting the pharmacokinetics and biodistributions. This work establishes the proof-of-concept of a new method for functionalizing lipid droplets and demonstrates that surface modification can have a significant impact on their interaction with cells, pharmacokinetics, and biodistribution.
authors.affiliation: Faculty of Pharmacy, University of Strasbourg, 74 route du Rhin 67401, Illkirch Cedex, France.|CNRS UMR 7199, Laboratoire de Conception et Application de Molécules Bioactives, équipe de Pharmacie Biogalénique, 74 route du Rhin 67401, Illkirch Cedex, France.|National Research Center, P.O. 12622, Cairo, Egypt.
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: Attia
authors.affiliation: Faculty of Pharmacy, University of Strasbourg, 74 route du Rhin 67401, Illkirch Cedex, France.|CNRS UMR 7199, Laboratoire de Conception et Application de Molécules Bioactives, équipe de Pharmacie Biogalénique, 74 route du Rhin 67401, Illkirch Cedex, France.
authors.forename: Sidy M
authors.initials: SM
authors.lastname: Dieng
authors.affiliation: Faculty of Pharmacy, University of Strasbourg, 74 route du Rhin 67401, Illkirch Cedex, France.|UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, équipe Nanochimie et Bioimagerie, 74 route du Rhin 67401, Illkirch Cedex, France.
authors.forename: Mayeul
authors.initials: M
authors.lastname: Collot
authors.affiliation: Faculty of Pharmacy, University of Strasbourg, 74 route du Rhin 67401, Illkirch Cedex, France.|UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, équipe Nanochimie et Bioimagerie, 74 route du Rhin 67401, Illkirch Cedex, France.
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Klymchenko
authors.affiliation: CERMEP Imagerie Vivant, Imaging Platform, Bron, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouillot
authors.affiliation: Institut Charles Sadron (ICS) UPR 22 CNRS, 67200, Strasbourg, France.
authors.forename: Christophe A
authors.initials: CA
authors.lastname: Serra
authors.affiliation: Institut Charles Sadron (ICS) UPR 22 CNRS, 67200, Strasbourg, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Schmutz
authors.affiliation: Institut Charles Sadron (ICS) UPR 22 CNRS, 67200, Strasbourg, France.
authors.forename: Meriem
authors.initials: M
authors.lastname: Er-Rafik
authors.affiliation: Faculty of Pharmacy, University of Strasbourg, 74 route du Rhin 67401, Illkirch Cedex, France.|CNRS UMR 7199, Laboratoire de Conception et Application de Molécules Bioactives, équipe de Pharmacie Biogalénique, 74 route du Rhin 67401, Illkirch Cedex, France.
authors.forename: Thierry F
authors.initials: TF
authors.lastname: Vandamme
authors.affiliation: Faculty of Pharmacy, University of Strasbourg, 74 route du Rhin 67401, Illkirch Cedex, France.|CNRS UMR 7199, Laboratoire de Conception et Application de Molécules Bioactives, équipe de Pharmacie Biogalénique, 74 route du Rhin 67401, Illkirch Cedex, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Anton
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D004655:Emulsions; D008055:Lipids / Q000737:chemistry / Q000493:pharmacokinetics; D008299:Maleic Anhydrides / Q000737:chemistry*; D051379:Mice
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D008299:Maleic Anhydrides
keywords: X-ray imaging; nanoemulsions; poly(maleic anhydride-alt-1-octadecene); surface functionalization; targeting