title: Microfluidic conceived Trojan microcarriers for oral delivery of nanoparticles.
abstract: In this study, we report on a novel method for the synthesis of poly(acrylamide) Trojan microparticles containing ketoprofen loaded poly(ethyl acrylate) or poly(methyl acrylate) nanoparticles. To develop these composite particles, a polymerizable nanoemulsion was used as a template. This nanoemulsion was obtained in an elongational-flow micromixer (μRMX) which was linked to a capillary-based microfluidic device for its emulsification into micron range droplets. Downstream, the microdroplets were hardened into Trojan particles in the size range of 213-308 μm by UV initiated free radical polymerization. The nanoemulsion size varied from 98 -132 nm upon changes in surfactant concentration and number of operating cycles in μRMX. SEM and confocal microscopy confirmed the Trojan morphology. Under SEM it was observed that the polymerization reduced the size of the nanoemulsion down to 20-32 nm for poly(ethyl acrylate) and 10-15 nm for poly(methyl acrylate) nanoparticles. This shrinkage was confirmed by cryo-TEM studies. We further showed that Trojan microparticles released embedded nanoparticles on contact with suitable media as confirmed by transmission electron microscopy. In a USP phosphate buffer solution of pH 6.8, Trojan microparticles containing poly(ethyl acrylate) nanoparticles released 35% of encapsulated ketoprofen over 24h. The low release of the drug was attributed to the overall low concentration of nanoparticles and attachment of some of nanoparticles to the poly(acrylamide) matrix. Thus, this novel method has shown possibility to develop Trojan particles convieniently with potential to deliver nanoparticles in the gastrointestinal tract.
authors.affiliation: Laboratory of Design and Application of Bioactive Molecules (CAMB), Faculty of Pharmacy, University of Strasbourg (UdS), Strasbourg, France; Institut Charles Sadron (ICS)-UPR 22 CNRS, Strasbourg, France; Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan. Electronic address: ikramglt@gmail.com.
authors.forename: Ikram Ullah
authors.initials: IU
authors.lastname: Khan
authors.affiliation: Institut Charles Sadron (ICS)-UPR 22 CNRS, Strasbourg, France; École Européenne de Chimie, Polymères et Matériaux (ECPM), Université de Strasbourg (UdS), Strasbourg, France. Electronic address: ca.serra@unistra.fr.
authors.forename: Christophe A
authors.initials: CA
authors.lastname: Serra
authors.affiliation: Laboratory of Design and Application of Bioactive Molecules (CAMB), Faculty of Pharmacy, University of Strasbourg (UdS), Strasbourg, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Anton
authors.affiliation: Institut Charles Sadron (ICS)-UPR 22 CNRS, Strasbourg, France.
authors.forename: Mériem
authors.initials: M
authors.lastname: Er-Rafik
authors.affiliation: Institut Charles Sadron (ICS)-UPR 22 CNRS, Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Blanck
authors.affiliation: Institut Charles Sadron (ICS)-UPR 22 CNRS, Strasbourg, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Schmutz
authors.affiliation: Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS)-UMR 7504 CNRS, F-67034 Strasbourg, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Kraus
authors.affiliation: Institute of Genetics and Molecular and Cellular Biology (IGBMC), CNRS/INSERM/Collège de France, Illkirch, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Messaddeq
authors.affiliation: Institute of Chemistry and Processes for Energy, Environment and Health (ICPEES-UMR 7515CNRS), University of Strasbourg (UdS), CNRS UMR 7515,Strasbourg, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Sutter
authors.affiliation: CNRS UMR 7213, Laboratoire de Biophotonique et Pharmacologie, 74 route du Rhin, 67401 Illkirch Cedex, France.
authors.forename: Halina
authors.initials: H
authors.lastname: Anton
authors.affiliation: CNRS UMR 7213, Laboratoire de Biophotonique et Pharmacologie, 74 route du Rhin, 67401 Illkirch Cedex, France.
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Klymchenko
authors.affiliation: Laboratory of Design and Application of Bioactive Molecules (CAMB), Faculty of Pharmacy, University of Strasbourg (UdS), Strasbourg, France.
authors.forename: Thierry F
authors.initials: TF
authors.lastname: Vandamme
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D064420:Drug-Related Side Effects and Adverse Reactions; D004655:Emulsions; D007660:Ketoprofen / Q000008:administration & dosage*; D044085:Microfluidics; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry*; D013501:Surface-Active Agents; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D004655:Emulsions; D007660:Ketoprofen; D011109:Polymethacrylic Acids; D013501:Surface-Active Agents; D000099166:Polyacrylamides; C478961:poly(ethylacrylate); C030613:polymethacrylic acid
keywords: Elongational flow; Nanoemulsions; Oral nanoparticle delivery; Poly(ethyl acrylate); Poly(methyl acrylate); Trojan