Microfluidic conceived Trojan microcarriers for oral delivery of nanoparticles

• Published in: International journal of pharmaceutics 2015-09, Vol.493 (1-2), p.7-15
• Main Authors: Khan, Ikram Ullah, Serra, Christophe A., Anton, Nicolas, Er-Rafik, Mériem, Blanck, C., Schmutz, Marc, Kraus, Isabelle, Messaddeq, Nadia, Sutter, Christophe, Anton, Halina, Klymchenko, Andrey S., Vandamme, Thierry F.
• Format: Article
• Language: English
• Subjects: Acrylic Resins - chemistry; Chemistry, Pharmaceutical; Drug Carriers - chemistry; Drug-Related Side Effects and Adverse Reactions; Elongational flow; Emulsions; Ketoprofen - administration & dosage; Life Sciences; Microfluidics; Microscopy, Electron, Scanning; Nanoemulsions; Nanoparticles - chemistry; Oral nanoparticle delivery; Particle Size; Poly(ethyl acrylate); Poly(methyl acrylate); Polymethacrylic Acids - chemistry; Surface-Active Agents; Trojan
• ISSN: 0378-5173; 1811-7775; 1873-3476; 1812-5700
• DOI: 10.1016/j.ijpharm.2015.06.028

[Display omitted] 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 213–308μm by UV initiated free radical polymerization. The nanoemulsion size varied from 98 –132nm 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 20–32nm for poly(ethyl acrylate) and 10–15nm 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.