1 Pharmaceutical nanotechnology 2 Microfluidic conceived Trojan microcarriers for oral delivery of 3 nanoparticles 4 Ikram Ullah Khan a,b,d, * Q1 , Christophe A. Serra b,c, *, Nicolas Anton a , Mériem Er-Rafik b , 5 Marc Schmutz b , Isabelle Kraus e , Nadia Messaddeq f , Christophe Sutter g , Halina Anton h , 6 Andrey S. Klymchenko h , Thierry F. Vandamme a 7 a Laboratory of Design and Application of Bioactive Molecules (CAMB), Faculty of Pharmacy, University of Strasbourg (UdS), Strasbourg, France 8 b Institut Charles Sadron (ICS)—UPR 22 CNRS, Strasbourg, France 9 c École Européenne de Chimie, Polymères et Matériaux (ECPM), Université de Strasbourg (UdS), Strasbourg, France 10 d Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan 11 e Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS)—UMR 7504 CNRS, F-67034 Strasbourg, France 12 f Institute of Genetics and Molecular and Cellular Biology (IGBMC), CNRS/INSERM/Collège de France, Illkirch, France 13 g Institute of Chemistry and Processes for Energy, Environment and Health (ICPEES—UMR 7515CNRS), University of Strasbourg (UdS), CNRS UMR 7515, 14 Strasbourg, France 15 h CNRS UMR 7213, Laboratoire de Biophotonique et Pharmacologie, 74 route du Rhin, 67401 Illkirch Cedex, France A R T I C L E I N F O Article history: Received 2 October 2014 Received in revised form 15 June 2015 Accepted 18 June 2015 Available online xxx Keywords: Trojan Nanoemulsions Elongational flow Poly(ethyl acrylate) Poly(methyl acrylate) Oral nanoparticle delivery A B S T R A C T In this study, we report on a novel Q3 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 (mRMX) 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 mm 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 mRMX. 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 24 h. 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. ã 2015 Published by Elsevier B.V. 16 1. Introduction 17 The oral route of administration is the most widely accepted 18 route for delivering active pharmaceutical ingredients. But poor 19 drug solubility, stability and absorption could lead to low 20 bioavailability in the blood stream (Ensign et al., 2012). Moreover, 21 in conventional dosage form, some drugs can also cause irritation 22 of gastrointestinal tract (GIT). One way to remove these hurdles is 23 by encapsulating the drug into micro- or nanoparticles. It has been 24 reported by many authors that these particles have the ability to 25 accumulate in inflamed areas and also reduce the toxic effect of 26 irritant drugs (Ranjha et al., 2009). 27 In nanotechnology, scientists manipulate drugs and polymers at 28 nanoscales (1–100 nm) that give unique chemical, physical and 29 biological properties, quite different from micro- and macro 30 systems (Anton et al., 2012; Shahzad, 2014). So far, nanotechnology 31 provided significant improvement in drug solubility, drug delivery, * Corresponding authors at: Institut Charles Q2 Sadron (ICS)—UPR 22 CNRS, Strasbourg, France. Fax: +33 36885270. E-mail addresses: ikramglt@gmail.com (I.U. Khan), ca.serra@unistra.fr (C.A. Serra). http://dx.doi.org/10.1016/j.ijpharm.2015.06.028 0378-5173/ ã 2015 Published by Elsevier B.V. International Journal of Pharmaceutics xxx (2015) xxx–xxx G Model IJP 14980 1–9 Please cite this article in press as: Khan, I.U., et al., Microfluidic conceived Trojan microcarriers for oral delivery of nanoparticles. Int J Pharmaceut (2015), http://dx.doi.org/10.1016/j.ijpharm.2015.06.028 Contents lists available at ScienceDirect International Journal of Pharmaceutics journal homepage: www.elsev ier.com/locate /ijpharm