title: Structured Biodegradable Polymeric Microparticles for Drug Delivery Produced Using Flow Focusing Glass Microfluidic Devices.
abstract: Biodegradable poly(DL-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microparticles with tunable size, shape, internal structure and surface morphology were produced by counter-current flow focusing in axisymmetric (3D) glass capillary devices. The dispersed phase was composed of 0.5-2 wt % polymer solution in a volatile organic solvent (ethyl acetate or dichloromethane) and the continuous phase was 5 wt % aqueous poly(vinyl alcohol) solution. The droplets with a coefficient of variation in dripping regime below 2.5% were evaporated to form polymeric particles with uniform sizes ranging between 4 and 30 μm. The particle microstructure and surface roughness were modified by adding nanofiller (montmorillonite nanoclay) or porogen (2-methylpentane) in the dispersed phase to form less porous polymer matrix or porous particles with golf-ball-like dimpled surface, respectively. The presence of 2-4 wt % nanoclay in the host polymer significantly reduced the release rate of paracetamol and prevented the early burst release, as a result of reduced polymer porosity and tortuous path for the diffusing drug molecules. Numerical modeling results using the volume of fluid-continuum surface force model agreed well with experimental behavior and revealed trapping of nanoclay particles in the dispersed phase upstream of the orifice at low dispersed phase flow rates and for 4 wt % nanoclay content, due to vortex formation. Janus PLA/PCL (polycaprolactone) particles were produced by solvent evaporation-induced phase separation within organic phase droplets containing 3% (v/v) PLA/PCL (30/70 or 70/30) mixture in dichloromethane. A strong preferential adsorption of Rhodamine 6G dye onto PLA was utilized to identify PLA portions of the Janus particles by confocal laser scanning microscopy (CLSM). Uniform hemispherical PCL particles were produced by dissolution of PLA domes with acetone.
authors.affiliation: Department of Chemical Engineering, Loughborough University , Loughborough, LE11 3TU, United Kingdom.
authors.forename: Ekanem E
authors.initials: EE
authors.lastname: Ekanem
authors.affiliation: School of Energy, Environment & Agrifood (SEEA), Department of Offshore, Process & Energy Engineering, Cranfield University , Cranfield, MK43 0AL, United Kingdom.
authors.forename: Seyed Ali
authors.initials: SA
authors.lastname: Nabavi
authors.affiliation: Department of Chemical Engineering, Loughborough University , Loughborough, LE11 3TU, United Kingdom.
authors.forename: Goran T
authors.initials: GT
authors.lastname: Vladisavljević
authors.affiliation: Department of Chemical and Process Engineering, Faculty of Engineering and Physical Sciences, University of Surrey , Guildford, GU2 7XH, United Kingdom.
authors.forename: Sai
authors.initials: S
authors.lastname: Gu
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004655:Emulsions / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D012212:Rheology; D014961:X-Ray Diffraction
chemical_list: D004655:Emulsions; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000082:Acetaminophen; C033616:poly(lactide)
keywords: Janus particle; biodegradable microspheres; drug delivery systems; hemispherical particle; microfluidic flow focusing; nanoclay; poly(lactic acid); poly(lactic-co-glycolic acid)