title: Silicon microfluidic flow focusing devices for the production of size-controlled PLGA based drug loaded microparticles.
abstract: The increasing realisation of the impact of size and surface properties on the bio-distribution of drug loaded colloidal particles has driven the application of micro fabrication technologies for the precise engineering of drug loaded microparticles. This paper demonstrates an alternative approach for producing size controlled drug loaded PLGA based microparticles using silicon Microfluidic Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of the flow focusing channel, microparticle size was successfully optimised by modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 μm and were highly monodisperse (coefficient of variation <5%). A comparison of Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional production techniques was also performed. MFFDs produced microparticles with a narrower size distribution profile, relative to the conventional approaches. In-vitro release kinetics of CsA was found to be influenced by the production technique, with the MFFD approach demonstrating the slowest rate of release over 7 days (4.99 ± 0.26%). Finally, MFFDs were utilised to produce pegylated microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly porous surface morphology and rapid CsA release, with 85 ± 6.68% CsA released after 24h. The findings from this study demonstrate the utility of silicon MFFDs for the precise control of size and surface morphology of PLGA based microparticles with potential drug delivery applications.
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Ireland.
authors.forename: Kieran
authors.initials: K
authors.lastname: Keohane
authors.affiliation: Tyndall National Institute, University College Cork, Ireland.
authors.forename: Des
authors.initials: D
authors.lastname: Brennan
authors.affiliation: Tyndall National Institute, University College Cork, Ireland.
authors.forename: Paul
authors.initials: P
authors.lastname: Galvin
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Ireland. Electronic address: brendan.griffin@ucc.ie.
authors.forename: Brendan T
authors.initials: BT
authors.lastname: Griffin
mesh_terms: D002626:Chemistry, Pharmaceutical; D016572:Cyclosporine / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D046210:Microfluidic Analytical Techniques; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D012825:Silicon / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D016572:Cyclosporine; D012825:Silicon
keywords: Ciclosporin A; Controlled release; Microfluidics; Monodisperse; PEG-PLGA; PLGA