title: Microfluidic conceived pH sensitive core-shell particles for dual drug delivery.
abstract: In current study, we report on the synthesis of core-shell microparticles for dual drug delivery by means of a two co-axial microfluidic device and online UV assisted free radical polymerization. Before developing pH-sensitive particles, ketoprofen loaded poly(methyl acrylate) core-ranitidine HCl loaded poly(acrylamide) shell particles were produced. Influence of inner and outer phases flow rates on particle size, shape, core diameter, shell thickness, and drug release properties was studied. All the particles were monodispersed with coefficient of variation below 5%. Furthermore, their diameter ranged from 100 to 151 μm by increasing continuous (Qc) to middle (Qm) phase flow rate ratio (Qc/Qm). Core diameter varied from 58 to 115 μm by decreasing middle (Qm) to inner (Qi) phase flow rate ratio (Qm/Qi) at constant continuous phase flow rate as confirmed by SEM images. It was observed that an optimum concentration of acrylamide (30 wt%) and an appropriate combination of surfactants were necessary to get core-shell particles otherwise Janus structure was obtained. FTIR confirmed the complete polymerization of core and shell phases. MTT assay showed variation in viability of cells under non-contact and contact conditions with less cytotoxicity for the former. Under non-contact conditions LD50 was 3.1mg/mL. Release studies in USP phosphate buffer solution showed simultaneously release of ketoprofen and ranitidine HCl for non pH-sensitive particles. However, release rates of ranitidine HCl and ketoprofen were higher at low and high pH respectively. To develop pH-sensitive particles for colon targeting, the previous shell phase was admixed with few weight percentage of pH sensitive carboxyethyl acrylate monomer. Core and shell contained the same hydrophobic and hydrophilic model drugs as in previous case. The pH-sensitive shell prevented the release of the two entrapped molecules at low pH while increasing significantly their release rate at higher pH with a maximum discharge at colonic pH of 7.4.
authors.affiliation: Laboratory of Design and Application of Bioactive Molecules (CAMB), Faculty of Pharmacy, University of Strasbourg (UdS), Strasbourg, France; Charles Sadron Institute (ICS)-UPR 22CNRS, Precision Macromolecular Chemistry Group (CMP), Strasbourg, France; University of Strasbourg (UdS), European Engineering School of Chemistry, Polymers and Materials Science (ECPM), Strasbourg, France; 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: Charles Sadron Institute (ICS)-UPR 22CNRS, Precision Macromolecular Chemistry Group (CMP), Strasbourg, France.
authors.forename: Lukas
authors.initials: L
authors.lastname: Stolch
authors.affiliation: Charles Sadron Institute (ICS)-UPR 22CNRS, Precision Macromolecular Chemistry Group (CMP), Strasbourg, France; University of Strasbourg (UdS), European Engineering School of Chemistry, Polymers and Materials Science (ECPM), 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: Laboratory of Design and Application of Bioactive Molecules (CAMB), Faculty of Pharmacy, University of Strasbourg (UdS), Strasbourg, France; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Russia.
authors.forename: Roman
authors.initials: R
authors.lastname: Akasov
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; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D007660:Ketoprofen / Q000737:chemistry; D051379:Mice; D044085:Microfluidics; D011109:Polymethacrylic Acids / Q000737:chemistry; D011899:Ranitidine / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D007660:Ketoprofen; D011109:Polymethacrylic Acids; D011899:Ranitidine; D000099166:Polyacrylamides; C030613:polymethacrylic acid
keywords: Cytotoxicity; Dual drug delivery; Microfluidics; Poly(acrylamide-co-carboxy ethyl acrylate); pH-sensitive.