Microfluidic conceived drug loaded Janus particles in side-by-side capillaries device.

A side-by-side capillaries microfluidic device was developed to fabricate drug loaded poly(acrylamide)/poly(methyl acrylate) Janus particles in the range of 59-240 μm by UV-assisted free radical polymerization. This system was characterized in terms of continuous and dispersed phases flow rates (Qc/Qd), monomer composition of the two compartments, surfactant nature and concentration, outlet tube diameter and UV intensity. These factors were adequately controlled to get different particle shapes ranging from core-shell to bi-compartmental particles. For the latter, a low surfactant concentration (0.75 wt.%) was necessary when the two dispersed phases were pumped at equal flow rate, while at high surfactant concentration, dispersed phases flow rates have to be changed. FTIR analysis suggested complete polymerization of monomers and cytotoxicity test showed these particles were biocompatible having LD 50 of 9 mg/mL. Both ketoprofen and sodium fluorescein were released in sustained release manner at pH 6.8 by following a diffusion type release mechanism. Drug release was faster for bigger particles and found to result from the irregular distribution of the two phases and indentation on bigger particles as revealed by SEM analysis. In comparison, sodium fluorescein release was slower which was attributed to low encapsulation but could be modified by decreasing crosslinker concentration.

[1]  W. Higuchi.  Diffusional Models Useful in Biopharmaceutics: Drug Release Rate Processes , 1967 .

[2]  S. Samanta,et al.  Coalescence of bubbles and stability of foams in aqueous solutions of Tween surfactants , 2011 .

[3]  H. Luo,et al.  Determination of the critical premicelle concentration, first critical micelle concentration and second critical micelle concentration of surfactants by resonance Rayleigh scattering method without any probe. , 2011, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[4]  M. Natu,et al.  Effects of drug solubility, state and loading on controlled release in bicomponent electrospun fibers. , 2010, International journal of pharmaceutics.

[5]  Ş. Sezgin,et al.  Polymerization of acrylamide initiated with Ce(IV)- and KMnO4-mercaptosuccinic acid redox systems in acid-aqueous medium , 2007 .

[6]  Volker Hessel,et al.  Microfluidic production of polymeric micro- and nanoparticles , 2013 .

[7]  M. Sowwan,et al.  Analysis Characterization and Some Properties of Polyacrylamide Copper Complexes , 2008 .

[8]  M. Blanco-Prieto,et al.  Polymeric Particulates to Improve Oral Bioavailability of Peptide Drugs , 2005, Molecules.

[9]  Gaurav Sharma,et al.  One-step fabrication of polymeric Janus nanoparticles for drug delivery. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[10]  G. Whitesides,et al.  Emulsification in a microfluidic flow-focusing device: effect of the viscosities of the liquids , 2008 .

[11]  Kam W Leong,et al.  Microfluidic synthesis of multifunctional Janus particles for biomedical applications. , 2012, Lab on a chip.

[12]  Kinam Park,et al.  Control of encapsulation efficiency and initial burst in polymeric microparticle systems , 2004, Archives of pharmacal research.

[13]  Hong Wang,et al.  Shape controllable microgel particles prepared by microfluidic combining external ionic crosslinking. , 2012, Biomicrofluidics.

[14]  Gabriela G Pereira,et al.  Microparticles of Aloe vera/vitamin E/chitosan: microscopic, a nuclear imaging and an in vivo test analysis for burn treatment. , 2014, European journal of pharmaceutics and biopharmaceutics.

[15]  Carlos Emmerson Ferreira da Costa,et al.  Thermal analysis characterization of PAAm-co-MC hydrogels , 2011 .

[16]  C. Hoyle,et al.  The kinetics of vinyl acrylate photopolymerization , 2003 .

[17]  I. Muhamad,et al.  Controlled drug release via minimization of burst release in pH-response kappa-carrageenan/polyvinyl alcohol hydrogels , 2013 .

[18]  G. Ayub,et al.  Assessment of palmitoyl and sulphate conjugated glycol chitosan for development of polymeric micelles. , 2013, BioImpacts : BI.

[19]  A. Nokhodchi,et al.  Microencapsulation of paracetamol: By various emulsion techniques using cellulose acetate phthalate , 2002 .

[20]  N. Anton,et al.  Continuous-flow encapsulation of ketoprofen in copolymer microbeads via co-axial microfluidic device: influence of operating and material parameters on drug carrier properties. , 2013, International journal of pharmaceutics.

[21]  P. Halling,et al.  Critical Micelle Concentrations of Nonionic Surfactants in Organic Solvents: Approximate Prediction with UNIFAC. , 2001, Journal of colloid and interface science.

[22]  J. Benoit,et al.  Why and how to prepare biodegradable, monodispersed, polymeric microparticles in the field of pharmacy? , 2011, International journal of pharmaceutics.

[23]  Rita B. Restani,et al.  Development of functional mesoporous microparticles for controlled drug delivery , 2010 .

[24]  Jinbao Guo,et al.  Microencapsulation of a functional dye and its UV crosslinking controlled releasing behavior , 2009 .

[25]  A. Lee,et al.  Droplet microfluidics. , 2008, Lab on a chip.

[26]  David S. Jones,et al.  Characterization of crosslinking effects on the physicochemical and drug diffusional properties of cationic hydrogels designed as bioactive urological biomaterials , 2005, The Journal of pharmacy and pharmacology.

[27]  I. Cho,et al.  Morphology of latex particles formed by poly(methyl methacrylate)-seeded emulsion polymerization of styrene , 1985 .

[28]  K. G. Desai,et al.  Preparation of cross-linked chitosan microspheres by spray drying: Effect of cross-linking agent on the properties of spray dried microspheres , 2005, Journal of microencapsulation.

[29]  M. Karjalainen,et al.  Improved entrapment efficiency of hydrophilic drug substance during nanoprecipitation of poly(I)lactide nanoparticles , 2004, AAPS PharmSciTech.

[30]  K. Leong,et al.  MR imaging of biodegradable polymeric microparticles: A potential method of monitoring local drug delivery , 2005, Magnetic resonance in medicine.

[31]  B. Cathala,et al.  Microfluidic generation and selective degradation of biopolymer-based Janus microbeads. , 2012, Biomacromolecules.

[32]  R. Mehvar,et al.  Preparation and release of ibuprofen from polyacrylamide gels. , 1999, Drug development and industrial pharmacy.

[33]  Chun-Xia Zhao,et al.  Multiphase flow microfluidics for the production of single or multiple emulsions for drug delivery. , 2013, Advanced drug delivery reviews.

[34]  Ikram Ullah Khan,et al.  Microfluidics: a focus on improved cancer targeted drug delivery systems. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[35]  R. K. Shah,et al.  Janus particles templated from double emulsion droplets generated using microfluidics. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[36]  L. Capretto,et al.  Microfluidic and lab-on-a-chip preparation routes for organic nanoparticles and vesicular systems for nanomedicine applications. , 2013, Advanced drug delivery reviews.