Continuous and controlled production of dexamethasone nanoparticles in a microfluidic system

Subject Areas :

payam zahedi ¹ , maryam tabatabai ² , morteza fathi pour ³ , amin sohrabi ⁴

1 - Assistant Prof. in Department of Polymer, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran.
2 - M.Sc. student in Department of Polymer, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran
3 - Professor in School of Electrical and Computer Engineering, College of Engineering, University of Tehran, Tehran, Iran
4 - M.Sc. student in Fouman School of Engineering, College of Engineering, University of Tehran, Tehran, Iran

Received: 2019-10-23 Accepted : 2020-05-20 Published : 2020-08-22

Keywords: nanoparticles, dexamethasone, Microfluidics, Crystallinity, Nanoprecipitation,

Abstract :

The aim of this work is to produce continuously dexamethasone nanoparticles (DEX NPs) in a microfluidic (MF) system via nanoprecipitation method to control particle size, possessing their physical structure, and enhancing the efficiency of this hydrophobic drug in physiological environments. In order to fabricate a MF chip, a series of microchannels with dimensions 1 cm in length, 200 μm in width, and 50 μm in depth are embedded using ultraviolet soft lithography on a sheet based on polydimethylsiloxane (PDMS), and then the laminar fluid flow ability is investigated through it. The effective factors on the optimized production of the drug NPs are determined by the design of experiment. In this line, the optimum values for drug solution concentration, surfactant concentration, drug solution flow rate, and non-solvent flow rate are 15 mg/ml, 1 mg/ml, 4.5 ml/h, and 8 ml/h, respectively. By adjusting these values the average sizes of DEX NPs are obtained 590 ± 20 nm based on the model and 500 ± 20 nm according to the experiments. In the following, the results of dynamic light scattering (DLS) test show the narrow size distribution of DEX NPs fabricated using the MF chip. Also, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) assays reveal that application of the MF system does not affect the crystallinity of the drug NPs and does not alter their structure after the process. Finally, MF-assisted DEX NPs sample shows the drug solubility rate of about 8-fold compared to the commercial powder ones

References:

[1] Vaculikova, E.; Pokorna, A.; Placha, D.; Pisarcik, M.; Dedkova, K.; Peikertova, P.; Devinsky, F.; Jampilek, J.; Journal of Nanoscience and Nanotechnology 19, 3031-3037, 2019.
[2] Merisko-Liversidge, E.; Liversidge, G.G.; Advanced Drug Delivery Reviews 63, 427-440, 2011.
[3] Rawal, M.; Singh, A.; Amiji, M.M.; Pharmaceutical Research 36, 153-157, 2019.
[4] Merisko-Liversidge, E.; Liversidge, G.G.; Cooper, E.R.; European Journal of Pharmaceutical Sciences 18, 113-210, 2003.
[5] Sia, S.K.; Whitesides, G.M.; Electrophoresis 24, 3563-3576, 2003.
[6] Song, Y.; Hormes, J.; Kumar, C.S.S.R.; Small 4, 698-711, 2008.
[7] Shamsi, M.; Zahedi, P.; Journal of Pharmaceutical Sciences 106, 3623-3630, 2017.
[8] Shamsi, M.; Zahedi, P.; Ghourchian, H.; Minaeian, S.; International Journal of Biological Macromolecules 99, 433-442, 2017.
[9] Becker, H.; Locascio, L.E.; Talanta 56, 267-287, 2002.
[10] McDonald, J.C.; Whitesides, G.M.; Accounts of Chemical Research 35, 491-499, 2002.
[11] Cohen, E.M.; "Analytical Profiles of Drug Substances", Elsevier, London, 1973.
[12] Ruy, C.R.; Silvia, S.; Acta Farmaceutica Bonaerense 22, 11-16, 2003.
[13] Chen, Y.; Li, J.; Kawazoe, N.; Chen, G.; Journal of Materials Chemistry B 5, 6801-6810, 2017.
[14] Gan, Q.; Zhu, J.; Yuan, Y.; Liu, H.; Qian, J.; Li, Y.; Liu, C.; Journal of Materials Chemistry B 3, 2050-2056, 2015.
[15] Sahle, F.F.; Gerecke, C.; Kleuser, B.; Bodmeier, R.; International Journal of Pharmaceutics 516, 21-31, 2017.
[16] Studer, K.; Decker, C.; Beck, E.; Schwalm, R.; Progress in Organic Coatings 48, 92-100, 2003.
[17] Chua, C.K.; Leong, K.F.; Lim, C.S., ''Rapid Prototyping: Principles and Applications'', World Scientific, Singapore; 2003.
[18] Yadollahi, R.; Vasilev, K.; Simovic, S.; Journal of Nanomaterials 2015, 1-13, 2015.
[19] Dizaj, S.M.; Vazifehasl, Z.; Salatin, S.; Adibkia, K.; Javadzadeh, Y.; Research in Pharmaceutical Sciences 10, 95-181, 2015.
[20] Thorat, A.A; Dalvi, S.V.; Chemical Engineering Journal 1,181-182, , 2012.

_||_