Trap Healing for High-Performance Low-Voltage Polymer Transistors and Solution-Based Analog Amplifiers on Foil.

Solution-processed semiconductors such as conjugated polymers have great potential in large-area electronics. While extremely appealing due to their low-temperature and high-throughput deposition methods, their integration in high-performance circuits has been difficult. An important remaining challenge is the achievement of low-voltage circuit operation. The present study focuses on state-of-the-art polymer thin-film transistors based on poly(indacenodithiophene-benzothiadiazole) and shows that the general paradigm for low-voltage operation via an enhanced gate-to-channel capacitive coupling is unable to deliver high-performance device behavior. The order-of-magnitude longitudinal-field reduction demanded by low-voltage operation plays a fundamental role, enabling bulk trapping and leading to compromised contact properties. A trap-reduction technique based on small molecule additives, however, is capable of overcoming this effect, allowing low-voltage high-mobility operation. This approach is readily applicable to low-voltage circuit integration, as this work exemplifies by demonstrating high-performance analog differential amplifiers operating at a battery-compatible power supply voltage of 5 V with power dissipation of 11 µW, and attaining a voltage gain above 60 dB at a power supply voltage below 8 V. These findings constitute an important milestone in realizing low-voltage polymer transistors for solution-based analog electronics that meets performance and power-dissipation requirements for a range of battery-powered smart-sensing applications.The authors gratefully acknowledge financial support from the Engineering and Physical Sciences Research Council (EPSRC) through the Centre for Innovative Manufacturing in Large Area Electronics (CIMLAE, program grant EP/K03099X/1) and the project Integration of Printed Electronics with Silicon for Smart sensor systems (iPESS). V.P. also acknowledges financial support from the Priority Academic Program Development of Jiangsu Higher Education Institutions Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and the Collaborative Innovation Center of Suzhou Nano Science and Technology

Study of mass and momentum transfer in diesel sprays base on X-ray mass distribution measurements and on a theoretical derivation

[EN] In this paper, a research aimed at quantifying mass and momentum transfer in the near-nozzle field of diesel sprays injected into stagnant ambient air is reported. The study combines X-ray measurements for two different nozzles and axial positions, which provide mass distributions in the spray, with a theoretical model based on momentum flux conservation, which was previously validated. This investigation has allowed the validation of Gaussian profiles for local fuel concentration and velocity near the nozzle exit, as well as the determination of Schmidt number at realistic diesel spray conditions. This information could be very useful for those who are interested in spray modeling, especially at high-pressure injection conditions. © 2010 Springer-Verlag.This work was partly sponsored by "Vicerrectorado de Investigacion, Desarrollo e Innovacion'' of the "Universidad Politecnica de Valencia'' in the frame of the project "Estudio del flujo en el interior de toberas de inyeccion Diesel'', reference no. 3150 and by "Generalitat Valenciana'' in the frame of the project with the same title and reference GV/2009/031. This support is gratefully acknowledged by the authors.Desantes, J.; Salvador Rubio, FJ.; López, JJ.; De La Morena, J. (2011). Study of mass and momentum transfer in diesel sprays base on X-ray mass distribution measurements and on a theoretical derivation. Experiments in Fluids. 50(2):233-246. https://doi.org/10.1007/s00348-010-0919-8S233246502Abramovich GN (1963) The theory of turbulent jets. MIT Press, Cambridge, MAAdler D, Lyn WT (1969) The evaporation and mixing of a liquid fuel spray in a Diesel air swirl. Proc Instn Mech Eng 184:171–180Coghe A, Cossali GE (1994) Phase Doppler characterisation of a Diesel spray injected into a high density gas under vaporisation regimes. In: 7th international symposium on application of laser techniques to fluid mechanics, LisbonCorreas D (1998) Theoretical and experimental study of isothermal Diesel free sprays (in Spanish). PhD Thesis, Universidad Politécnica de ValenciaCossali GE (2001) An integral model for gas entrainment into full cone sprays. J Fluid Mech 439:353–366Dent JC (1971) A basis for the comparison of various experimental methods for studying spray penetration. SAE Paper 710571Desantes JM, Payri R, Salvador FJ, Gil A (2006a) Deduction and validation of a theoretical model for a free diesel Spray. Fuel 85:910–917Desantes JM, Arrègle J, López JJ, Cronhjort A (2006b) Scaling laws for free turbulent gas jets and Diesel-like sprays. Atomization Spray 16:443–473Desantes JM, Payri R, García JM, Salvador FJ (2007) A contribution to the understanding of isothermal diesel spray dynamics. Fuel 86:1093–1101Dumouchel C (2008) On the experimental investigation on primary atomization of liquid streams. Exp Fluids 45:371–422Heimgärtner C, Leipertz A (2000) of the primary spray break-up close to the nozzle of a common-rail high pressure diesel injection system. SAE Paper 2000-01-1799Hinze JO (1975) Turbulence. McGraw Hill, New YorkHiroyasu H, Arai M (1990) Structures of fuel sprays in diesel engines. SAE Paper 900475Jawad B, Gulari E, Henein NA (1992) Characteristics of intermittent fuel sprays. Combust Flame 88:384–396Lefèbvre AH (1989) Atomization and sprays. Hemisphere, New YorkLeick P, Riedel T, Bittlinger G, Powell CF, Kastengren AL, Wang J (2007) X-Ray measurements of the mass distribution in the dense primary break-up region of the spray from a standard multi-hole common-rail diesel injection system. In: Proc 21st ILASS (Europe)Linne M, Paciaroni M, Hall T, Parker T (2006) Ballistic imaging of the near field in a diesel spray. Exp Fluids 40:836–846Naber J, Siebers DL (1996) Effects of gas density and vaporisation on penetration and dispersion of diesel sprays. SAE Paper 960034Payri F, Bermúdez V, Payri R, Salvador FJ (2004) The influence of cavitation on the internal flow and the Spray characteristics in diesel injection nozzles. Fuel 83:419–431Payri R, García JM, Salvador FJ, Gimeno J (2005) Using spray momentum flux measurements to understand the influence of diesel nozzle geometry on spray characteristics. Fuel 84:551–561Payri R, Tormos B, Salvador FJ, Araneo L (2008) Spray droplet velocity characterization for convergent nozzles with three different diameters. Fuel 87:3176–3182Post S, Iyer V, Abraham J (2000) A study of near-field entrainment in gas jets and sprays under diesel conditions. ASME J Fluids Eng 122:385–395Prasad CMV, Kar S (1976) An investigation on the diffusion of momentum and mass of fuel in a diesel fuel spray. ASME J Eng Power 76-DGP-1:1–11Rajaratnam N (1976) Turbulent jets. Elsevier, AmsterdamRamirez AI, Som S, Aggarwal SK, Kastengren AL, El-Hannouny EM, Longman DE, Powell CF (2009) Quantitative X-ray measurements of high-pressure fuel sprays from a production heavy duty diesel injector. Exp Fluids 47:119–134Reitz RD, Bracco FV (1982) Mechanism of atomisation of a liquid jet. Phys Fluids 25(10):1730–1742Ricou FP, Spalding DB (1961) Measurements of entrainment by axisymmetrical turbulent jets. J Fluid Mech 11:21–32Rife J, Heywood JB (1974) Photographic and performance studies of diesel combustion with a rapid compression machine. SAE Paper 740948Roisman IV, Tropea C (2001) Flux measurements in sprays using phase doppler techniques. Atomization Spray 11:667–699Roisman IV, Araneo L, Tropea C (2007) Effect of ambient pressure on penetration of a diesel spray. Int J Multiphase Flow 33(8):904–920Saliba R, Baz I, Champoussin JC, Lance M, Marié JL (2004) Cavitation effect on the near nozzle spray development in high-pressure diesel injection. In: Proc 19th ILASS (Europe)Schlichting H (1978) Boundary layer theory. McGraw Hill, New YorkSinnamon JF, Lancaster DR, Stiener JC (1980) An experimental and analytical study of engine fuel spray trajectories. SAE Paper 800135Sou A, Hosokawa S, Tomiyama A (2007) Effects of cavitation in a nozzle on liquid jet atomization. Int J Heat Mass Tran 50(17–18):3575–3582Spalding DB (1979) Combustion and mass transfer. Pergamon Press, New YorkSubramaniam S (2001) Statistical modelling of a spray as using the droplet distribution function. Phys Fluids 13(3):624–642Tanner FX, Feigl A, Ciatti SA, Powell CF, Cheong S-K, Liu J, Wang J (2006) Structure of high-velocity dense sprays in the near-nozzle region. Atomization Spray 16:579–597Way RJB (1977) Investigation of interaction between swirl and jets in direct injection diesel engines using a water model. SAE Paper 770412Wu KJ, Santavicca DA, Bracco FV (1984) LDV measurements of drop velocity in diesel-type sprays. AAIA J 22(9):1263–1270Wu KJ, Reitz RD, Bracco FV (1986) Measurements of drop size at the spray edge near the nozzle in atomising liquid jets. Phys Fluids 29(4):941–951Yue Y, Powell CF, Poola R, Wang J, Schaller JK (2001) Quantitative measurements of diesel fuel spray characteristics in the near-nozzle region using X-ray absorption. Atomization Spray 11(4):471–49

Pulmonary Delivery of Proteins Using Nanocomposite Microcarriers.

In this study, Taguchi design was used to determine optimal parameters for the preparation of bovine serum albumin (BSA)-loaded nanoparticles (NPs) using a biodegradable polymer poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL). NPs were prepared, using BSA as a model protein, by the double emulsion evaporation process followed by spray-drying from leucine to form nanocomposite microparticles (NCMPs). The effect of various parameters on NP size and BSA loading were investigated and dendritic cell (DC) uptake and toxicity. NCMPs were examined for their morphology, yield, aerosolisation, in vitro release behaviour and BSA structure. NP size was mainly affected by the polymer mass used and a small particle size ≤500 nm was achieved. High BSA (43.67 ± 2.3 μg/mg) loading was influenced by BSA concentration. The spray-drying process produced NCMPs (50% yield) with a porous corrugated surface, aerodynamic diameter 1.46 ± 141 μm, fine particle dose 45.0 ± 4.7 μg and fine particle fraction 78.57 ± 0.1%, and a cumulative BSA release of 38.77 ± 3.0% after 48 h. The primary and secondary structures were maintained as shown by sodium dodecyl sulphate poly (acrylamide) gel electrophoresis and circular dichroism. Effective uptake of NPs was seen in DCs with >85% cell viability at 5 mg/mL concentration after 4 h. These results indicate the optimal process parameters for the preparation of protein-loaded PGA-co-PDL NCMPs suitable for inhalation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci

Computational investigation of diesel nozzle internal flow during the complete injection event

[EN] Currently, diesel engines are calibrated using more and more complex multiple injection strategies. Under these conditions, the characteristics of the flow exiting the fuel injector are strongly affected by the transient interaction between the needle, the sac volume and the orifices, which are not yet clear. In the current paper, a methodology combining a 1D injector model and 3D-CFD simulations is proposed. First, the characteristics of the nozzle flow have been experimentally assessed in transient conditions by means of injection rate and momentum flux measurements. Later, the 3D-CFD modeling approach has been validated at steady-state fixed lift conditions. Finally, a previously developed 1D injector model has been used to extract the needle lift profiles and transient pressure boundary conditions used for the full-transient 3D-CFD simulations, using adaptive mesh refinement (AMR) strategies to be able to simulate the complete injection rate starting from 1 mu m lift.This work was partly sponsored by "Ministerio de Economia y Competitividad'', of the Spanish Government, in the frame of the Project "Estudio de la interaccion chorro-pared en condiciones realistas de motor'', Reference TRA2015-67679-c2-1-R. The authors would like also to thank the computer resources, technical expertise and assistance provided by Universidad de Valencia in the use of the supercomputer "Tirant''. Mr. Jaramillo's Thesis is funded by "Conselleria d'Educacio, Cultura i Esports'' of Generalitat Valenciana in the frame of the program "Programa VALI + D para investigadores en formacion, Reference ACIF/2015/040.Salvador, FJ.; De La Morena, J.; Bracho Leon, G.; Jaramillo-Císcar, D. (2018). Computational investigation of diesel nozzle internal flow during the complete injection event. Journal of the Brazilian Society of Mechanical Sciences and Engineering. 40(3):153-167. https://doi.org/10.1007/s40430-018-1074-zS153167403Hall CAS, Lambert JG, Balogh SB (2014) EROI of different fuels and the implications for society. Energy Policy 64:141–152. https://doi.org/10.1016/j.enpol.2013.05.049Lujan JM, Tormos B, Salvador FJ, Gargar K (2009) Comparative analysis of a DI diesel engine fuelled with biodiesel blends during the European MVEG-A cycle: preliminary study (I). Biomass Bioenergy 33:941–947. https://doi.org/10.1016/j.biombioe.2009.02.004Pickett LM, Siebers DL (2004) Soot in diesel fuel jets: effects of ambient temperature, ambient density, and injection pressure. Combust Flame 138:114–135. https://doi.org/10.1016/j.combustflame.2004.04.006Dec JE (1997) A Conceptual Model of DI Diesel Combustion Based on Laser-Sheet Imaging. SAE Tech. Pap. 970873Wang X, Huang Z, Zhang W et al (2011) Effects of ultra-high injection pressure and micro-hole nozzle on flame structure and soot formation of impinging diesel spray. Appl Energy 88:1620–1628. https://doi.org/10.1016/j.apenergy.2010.11.035Sayin C, Gumus M, Canakci M (2013) Influence of injector hole number on the performance and emissions of a di diesel engine fueled with biodiesel-diesel fuel blends. Appl Therm Eng 61:121–128. https://doi.org/10.1016/j.applthermaleng.2013.07.038Mohan B, Yang W, Chou SK (2013) Fuel injection strategies for performance improvement and emissions reduction in compression ignition engines—A review. Renew Sustain Energy Rev 28:664–676. https://doi.org/10.1016/j.rser.2013.08.051Payri R, Salvador FJ, Gimeno J, De la Morena J (2011) Influence of injector technology on injection and combustion development, Part 1: hydraulic characterization. Appl Energy 88:1068–1074. https://doi.org/10.1016/j.apenergy.2010.10.012Park SW, Kim JW, Lee CS (2006) Effect of injector type on fuel-air mixture formation of high-speed diesel sprays. Proc Inst Mech Eng D 220:647–659. https://doi.org/10.1243/09544070D20304Moon S, Komada K, Sato K et al (2015) Ultrafast X-ray study of multi-hole GDI injector sprays: effects of nozzle hole length and number on initial spray formation. Exp Therm Fluid Sci 68:68–81. https://doi.org/10.1016/j.expthermflusci.2015.03.027Powell CF, Kastengren AL, Liu Z, Fezzaa K (2010) The effects of diesel injector needle motion on spray structure. J Eng Gas Turbines Power 133:12802. https://doi.org/10.1115/1.4001073Huang W, Moon S, Ohsawa K (2016) Near-nozzle dynamics of diesel spray under varied needle lifts and its prediction using analytical model. Fuel 180:292–300. https://doi.org/10.1016/j.fuel.2016.04.042Sun Z-Y, Li G-X, Chen C et al (2015) Numerical investigation on effects of nozzle’s geometric parameters on the flow and the cavitation characteristics within injector’s nozzle for a high-pressure common-rail DI diesel engine. Energy Convers Manag 89:843–861. https://doi.org/10.1016/j.enconman.2014.10.047Devassy BM, Habchi C, Daniel E (2015) Atomization modelling of liquid jets using a two-surface density approach. At Sprays 25:47–80Moon S, Gao Y, Park S et al (2015) Effect of the number and position of nozzle holes on in- and near-nozzle dynamic characteristics of diesel injection. Fuel 150:112–122. https://doi.org/10.1016/j.fuel.2015.01.097Payri R, Salvador FJ, Carreres M, De la Morena J (2016) Fuel temperature influence on the performance of a last generation common-rail diesel ballistic injector. Part II: 1D model development, validation and analysis. Energy Convers Manag 114:376–391. https://doi.org/10.1016/j.enconman.2016.02.043Plamondon E, Seers P (2014) Development of a simplified dynamic model for a piezoelectric injector using multiple injection strategies with biodiesel/diesel-fuel blends. Appl Energy 131:411–424. https://doi.org/10.1016/j.apenergy.2014.06.039Postrioti L, Malaguti S, Bosi M et al (2014) Experimental and numerical characterization of a direct solenoid actuation injector for diesel engine applications. Fuel 118:316–328. https://doi.org/10.1016/j.fuel.2013.11.001Desantes JM, Salvador FJ, Lopez JJ, De la Morena J (2011) Study of mass and momentum transfer in diesel sprays based on X-ray mass distribution measurements and on a theoretical derivation. Exp Fluids 50:233–246. https://doi.org/10.1007/s00348-010-0919-8De la Morena J, Neroorkar K, Plazas AH et al (2013) Numerical analysis of the influence of diesel nozzle design on internal flow characteristics for 2-valve diesel engine application. At Sprays 23:97–118. https://doi.org/10.1615/AtomizSpr.2013006361Duke DJ, Schmidt DP, Neroorkar K et al (2013) High-resolution large eddy simulations of cavitating gasoline-ethanol blends. Int J Engine Res 14:578–589. https://doi.org/10.1177/1468087413501824Mitroglou N, McLorn M, Gavaises M et al (2014) Instantaneous and ensemble average cavitation structures in diesel micro-channel flow orifices. Fuel 116:736–742. https://doi.org/10.1016/j.fuel.2013.08.060Wang X, Li K, Su W (2012) Experimental and numerical investigations on internal flow characteristics of diesel nozzle under real fuel injection conditions. Exp Therm Fluid Sci 42:204–211. https://doi.org/10.1016/j.expthermflusci.2012.04.022Sou A, Pratama RH (2016) Effects of asymmetric inflow on cavitation in fuel injector and discharged liquid jet. At Sprays 26:939–959. https://doi.org/10.1615/AtomizSpr.2015013501Xue Q, Battistoni M, Powell CF et al (2015) An Eulerian CFD model and X-ray radiography for coupled nozzle flow and spray in internal combustion engines. Int J Multiph Flow 70:77–88. https://doi.org/10.1016/j.ijmultiphaseflow.2014.11.012Castilla R, Gamez-Montero PJ, Ertrk N et al (2010) Numerical simulation of turbulent flow in the suction chamber of a gearpump using deforming mesh and mesh replacement. Int J Mech Sci 52:1334–1342. https://doi.org/10.1016/j.ijmecsci.2010.06.009Parlak Z, Engin T (2012) Time-dependent CFD and quasi-static analysis of magnetorheological fluid dampers with experimental validation. Int J Mech Sci 64:22–31. https://doi.org/10.1016/j.ijmecsci.2012.08.006Chiatti G, Chiavola O, Palmieri F (2009) Spray modeling for diesel engine performance analysis. SAE Tech Pap 2009-01-0835. https://doi.org/10.4271/2009-01-0835Marcer R, Audiffren C, Viel A, et al (2010) Coupling 1D system AMESim and 3D CFD EOLE models for diesel injection simulation Renault. In: ILASS—Eur. 2010, 23rd Annu. Conf. Liq. At. Spray Syst., pp 1–10Desantes JM, Salvador FJ, Carreres M, Martínez-López J (2014) Large-eddy simulation analysis of the influence of the needle lift on the cavitation in diesel injector nozzles. Proc Inst Mech Eng D 229:407–423. https://doi.org/10.1177/0954407014542627Battistoni M, Xue Q, Som S (2016) Large-eddy simulation (LES) of spray transients: start and end of injection phenomena. Oil Gas Sci Technol 71:24. https://doi.org/10.2516/ogst/2015024CONVERGE is a trade mark of convergent science. https://convergecfd.comMacian V, Bermúdez V, Payri R, Gimeno J (2003) New technique for determination of internal geometry of a diesel nozzle with the use of silicone methodology. Exp Tech 27:39–43. https://doi.org/10.1111/j.1747-1567.2003.tb00107.xDabiri S, Sirignano WA, Joseph DD (2007) Cavitation in an orifice flow. Phys Fluids 19:72112. https://doi.org/10.1063/1.2750655Mohan B, Yang W, Chou SK (2014) Cavitation in injector nozzle holes—a parametric study. Eng Appl Comput Fluid Mech 8:70–81Salvador FJ, Hoyas S, Novella R, Martinez-Lopez J (2011) Numerical simulation and extended validation of two-phase compressible flow in diesel injector nozzles. Proc Inst Mech Eng D 225:545–563. https://doi.org/10.1177/09544070JAUTO1569Som S, Longman DE, Ramirez AI, Aggarwal S (2012) Influence of nozzle orifice geometry and fuel properties on flow and cavitation characteristics of a diesel injector. In: Fuel Inject. Automot. Eng., pp 112–126Desantes JM, Salvador FJ, Carreres M, Jaramillo D (2015) Experimental characterization of the thermodynamic properties of diesel fuels over a wide range of pressures and temperatures. SAE Int J Fuels Lubr 8:2015-01-0951. https://doi.org/10.4271/2015-01-0951Bosch W (1966) The fuel rate indicator: a new measuring instrument for display of the characteristics of individual injection. SAE Pap. 660749Payri R, Salvador FJ, Gimeno J, Bracho G (2008) A new methodology for correcting the signal cumulative phenomenon on injection rate measurements. Exp Tech 32:46–49. https://doi.org/10.1111/j.1747-1567.2007.00188.xPayri F, Payri R, Salvador FJ, Martínez-López J (2011) A contribution to the understanding of cavitation effects in diesel injector nozzles through a combined experimental and computational investigation. Comput Fluids 58:88–101. https://doi.org/10.1016/j.compfluid.2012.01.005Lichtarowicz AK, Duggins RK, Markland E (1965) Discharge coefficients for incompressible non-cavitating flow through long orifices. J Mech Eng Sci 7:210–219. https://doi.org/10.1243/JMES_JOUR_1965_007_029_02Lopez JJ, Salvador FJ, De la Garza OA, Arrègle J (2012) Characterization of the pressure losses in a common rail diesel injector. Proc Inst Mech Eng D 226:1697–1706. https://doi.org/10.1177/0954407012447020Salvador FJ, Carreres M, Jaramillo D, Martínez-López J (2015) Comparison of microsac and VCO diesel injector nozzles in terms of internal nozzle flow characteristics. Energy Convers Manag 103:284–299. https://doi.org/10.1016/j.enconman.2015.05.062LMS (2010) Imagine.Lab AMESim v.10. User’s manualPayri R, Salvador FJ, Martí-Aldaraví P, Martínez-López J (2012) Using one-dimensional modeling to analyze the influence of the use of biodiesels on the dynamic behavior of solenoid-operated injectors in common rail systems: detailed injection system model. Energy Convers Manag 54:90–99. https://doi.org/10.1016/j.enconman.2011.10.00

β-Hydroxy-β-Methylbutyrate (HMB) Normalizes Dexamethasone-Induced Autophagy-Lysosomal Pathway in Skeletal Muscle

Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.This project has been funded by Abbott Nutrition R&D

Pulmonary delivery of Nanocomposite Microparticles (NCMPs) incorporating miR-146a for treatment of COPD.

The treatment and management of COPD by inhalation to the lungs has emerged as an attractive alternative route to oral dosing due to higher concentrations of the drug being administered to site of action. In this study, Nanocomposite Microparticles (NCMPs) of microRNA (miR-146a) containing PGA-co-PDL nanoparticles (NPs) for dry powder inhalation were formulated using l-leucine and mannitol. The spray-drying (Buchi B290) process was optimised and used to incorporate NPs into NCMPs using mix of l-leucine and mannitol excipients in different ratios (F1; 100:0% w/w, F2; 75:25% w/w, F3; 50:50% w/w, F4; 25:75% w/w, F5; 0:100% w/w) to investigate yield %, moisture content, aerosolisation performance and miR-146a biological activity. The optimum condition was performed at feed rate 0.5 ml/min, aspirator rate 28 m3/h, atomizing air flow rate 480 L/h, and inlet drying temperature 70 °C which produced highest yield percentage and closest recovered NPs size to original prior spray-drying. The optimum formulation (F4) had a high yield (86.0 ± 15.01%), recovered NPs size after spray-drying 409.7 ± 10.05 nm (initial NPs size 244.8 ± 4.40 nm) and low moisture content (2.02 ± 0.03%). The aerosolisation performance showed high Fine Particle Fraction (FPF) 51.33 ± 2.9%, Emitted Dose (ED) of 81.81 ± 3.0%, and the mass median aerodynamic diameter (MMAD) was ≤5 µm suggesting a deposition in the respirable region of the lungs. The biological activity of miR-146a was preserved after spray-drying process and miR-146a loaded NCMPs produced target genes IRAK1 and TRAF6 silencing. These results indicate the optimal process parameters for the preparation of NCMPs of miR-146a-containing PGA-co-PDL NPs suitable for inhalation in the treatment and management of COPD