Articles
All articles | Recent articles
3D Focalization Microfluidic Device Built with LTCC Technology for Nanoparticle Generation using Nanoprecipitation Route
H.C. Gomez1, M.R. Gongora-Rubio2, B.O. Agio2, J. de Novais Schianti2, V. Tiemi Kimura2, A- Marim de Oliveira2, L. Wasnievski da Silva de Luca Ramos2, A.C. Seabra1
1 Escola Politécnica da Universidade de São Paulo (USP), Laboratório de Sistemas Integráveis, Av. Prof. Luciano Gualberto, 158, 05508 – 900, São Paulo, Brasil
2 Instituto de Pesquisas Tecnológicas do Estado de São Paulo (IPT), Núcleo de Bionanomanufatura, Av. Prof. Almeida prado, 532, 05508-901, São Paulo, Brasil
received September 18, 2015, received in revised form November 11, 2015, accepted November 25, 2015
Vol. 6, No. 4, Pages 329-338 DOI: 10.4416/JCST2015-00062
Abstract
Nanoprecipitation is a nanonization technique used for generating nanoparticles. Fields like pharmaceuticals and fine chemistry make use of such techniques. Typically, bulky batch mechanical processes are used, but these result in a high polydispersity index of the generated nanoparticles, poor particle size reproducibility and energy waste.
LTCC-based microsystem technologies allow the implementation of different unitary operations for the chemical process, making it an enabling technology for miniaturization. In fact, LTCC microfluidic reactors have recently been used to produce micro- and nanoparticles with excellent control of size distribution and morphology.
The present work reports on the performance of two 3D LTCC flow-focusing microfluidic devices designed to fabricate polymeric nanocapsules for hydrocortisone acetate drug encapsulation, based on the nanoprecipitation route. Monomodal submicron and nanometer particles were obtained. Zetasizer-measured sizes (Tp) were in the range from 162.2 nm to 459.1 nm with a polydispersity index (PDI) ranging from 0.102 to 0.235.
Download Full Article (PDF)
Keywords
Nanoprecipitation, fluid flow focusing, LTCC, nanoparticles.
References
1 Stainmesse, S., Orecchioni, A.M., Nakache, E., Puisieux, F., Fessi, H.: Formation and stabilization of a biodegradable polymeric colloidal suspension of nanoparticles, Colloid. Polym. Sci., 273, 505 – 511, (1995).
2 Nagavarma, B.V.N., Yadav, H.K.S., Ayaz, A., Vasudha, L.S., Shivakumar, H.G.: Different techniques for preparation of polymeric nanoparticles – A review, Asian J. Pharm. Clin. Res., 5, 16 – 23, (2012).
3 Chen, H., Khemtong, C., Yang, X., Chang, S., Gao, J.: Nanonization strategies for poorly water-soluble drugs, Drug Discov. Today, 16, 354 – 360, (2011).
4 Schubert, S., Delaney Jr, J.T., Schubert, U.S.: Nanoprecipitation and nanoformulation of polymers: From history to powerful possibilities beyond poly(lactic acid), Soft Matter, 7, 1581 – 1588, (2011).
5 Lepeltier, E., Bourgaux, C., Couvreur, P.: Nanoprecipitation and the "Ouzo effect": Application to drug delivery devices, Adv. Drug Deliv. Rev., 71, 86 – 97, (2014).
6 Chan, H.K., Kwok, P.C.L.: Production methods for nanodrug particles using the bottom-up approach, Adv. Drug Deliv. Rev., 63, 406 – 416, (2011).
7 Barton, A.F.M.: CRC Handbook of solubility parameters and other cohesion parameters, Second Edition: Taylor & Francis, 1991.
8 Hansen C.M.: Hansen solubility parameters: A user's handbook, Second Edition ed.: CRC Press, 2007.
9 van Krevelen, D.W.: Properties of polymers: Elsevier Science, 2012.
10 van Krevelen, D.W., te Nijenhuis, K.: Properties of polymers: Their correlation with chemical structure; their numerical estimation and prediction from additive group contributions: Elsevier Science, 2009.
11 Wang, S.H., Liu, J.H., Pai, C.T., Chen, W., Chung, P.T., Chiang, A.S.T., Chang, S.J.: Hansen solubility parameter analysis on the dispersion of zirconia nanocrystals, J. Colloid Interf. Sci., 407, 140 – 147, (2013).
12 Othman, R., Vladisavljević, G.T., Hemaka Bandulasena, H.C., Nagy, Z.K.: Production of polymeric nanoparticles by micromixing in a co-flow microfluidic glass capillary device, Chem. Eng. J., 280, 316 – 329, (2015).
13 Ali, H.S.M., Blagden, N., York, P., Amani, A., Brook, T.: Artificial neural networks modelling the prednisolone nanoprecipitation in microfluidic reactors, Eur. J. Pharm. Sci., 37, 514 – 522, (2009).
14 Ali, H.S.M., York, P., Ali, A.M.A., Blagden, N.: Hydrocortisone nanosuspensions for ophthalmic delivery: A comparative study between microfluidic nanoprecipitation and wet milling, J. Control. Release, 149, 175 – 181, (2011).
15 Wang, J.X., Zhang, Q.X., Zhou, Y., Shao, L., Chen, J.F.: Microfluidic synthesis of amorphous cefuroxime axetil nanoparticles with size-dependent and enhanced dissolution rate, Chem. Eng. J., 162, 844 – 851, (2010).
16 Ali, H.S.M., York, P., Blagden, N.: Preparation of hydrocortisone nanosuspension through a bottom-up nanoprecipitation technique using microfluidic reactors, Int. J. Pharma., 375, 107 – 113, (2009).
17 Aghajani, M., Shahverdi, A.R., Amani, A.: The use of artificial neural networks for optimizing polydispersity index (PDI) in nanoprecipitation process of acetaminophen in microfluidic devices, AAPS PharmSciTech, 13, 1293 – 1301, (2012).
18 Karnik, R., Gu, F., Basto, P., Cannizzaro, C., Dean, L., Kyei-Manu, W., Langer, R., Farokhzad, O.C.: Microfluidic platform for controlled synthesis of polymeric nanoparticles, Nano Lett., 8, 2906 – 2912, (2008).
19 Valencia, P., Basto, P., Gu, F., Zhang, L., Cannizzaro, C., Langer, R., Farokhzad, O., Karnik, R.: Novel synthesis of polymeric nanoparticles for drug delivery applications using microfluidic rapid mixing, in 12th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2008, San Diego, CA, 2008, 1513 – 1515.
20 Schianti, J.N., Cerize, N.N.P., de Oliveira, A.M., Derenzo, S., Seabra, A.C., Góngora-Rubio, M.R.: Rifampicin nanoprecipitation using flow focusing microfluidic device, J. Nanomed.Nanotechnol., 4, (2013).
21 Capretto, L., Cheng, W., Carugo, D., Katsamenis, O.L., Hill, M., Zhang, X.: Mechanism of co-nanoprecipitation of organic actives and block copolymers in a microfluidic environment, Nanotechnology, 23, (2012).
22 Capretto, L., Carugo, D., Cheng, W., Hill, M., Zhang, X.: Continuous-flow production of polymeric micelles in microreactors: experimental and computational analysis, J. Colloid Interf. Sci., 357, 243 – 251, (2011).
23 Cobas Gomez, H., Seabra, A.C., Araujo Feitosa, V., de Novais Schianti, J., Marim de Oliveira, A., Wasnievski da Silva de Luca Ramos, L., Gongora-Rubio, M. R.: Development of a LTCC micro spray dryer, in sensors (IBERSENSOR), 2014 IEEE 9th Ibero-American Congress on, 2014, 1 – 5.
24 Rhee, M., Valencia, P.M., Rodriguez, M.I., Langer, R.S., Farokhzad, O.C., Karnik, R.: 3D hydrodynamic focusing for confined precipitation of nanoparticles within microfluidic channels, in 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2010, MicroTAS 2010, Groningen, 2010, 992 – 994.
25 Rhee, M., Valencia, P.M., Rodriguez, M.I., Langer, R., Farokhzad, O.C., Karnik, R.: Synthesis of size-tunable polymeric nanoparticles enabled by 3D hydrodynamic flow focusing in single-layer microchannels, Adv. Mater., 23, H79 – H83, (2011).
26 Schianti, J.N., Cerize, N.P.N., Oliveira, A.M., Derenzo, S., Góngora-Rubio, M.R.: 3-D LTCC microfluidic device as a tool for studying nanoprecipitation, 8th Ibero-American Congress on Sensors, IBERSENSOR 2012, vol. 421, 2013.
27 Lim, J.M., Bertrand, N., Valencia, P.M., Rhee, M., Langer, R., Jon, S., Farokhzad, O.C., Karnik, R.: Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D flow focusing towards in vivo study, Nanomedicine: NBM, 10, 401 – 409, (2014).
28 Gongora-Rubio, M.R., Schianti, J.d.N., Cobas, H., Teves, A. d. C.: LTCC-3D coaxial flow focusing microfluidic reactor for micro and nanoparticle fabrication and production scale-out, Journal of Microelectronic & Electronic Packaging, 10, (2013).
29 Gongora-Rubio, M.R., Espinoza-Vallejos, P., Sola-Laguna, L., Santiago-Avilés, J.J.: Overview of low temperature co-fired ceramics tape technology for meso-system technology (MsST), Sensor. Actuat. A.-Phys, 89, 222 – 241, (2001).
30 Dias, A.R.M.: Síntese e caracterização de copolímeros em bloco anfifílicos, por transesterificação, com redução de massa molar da poli(ε-caprolactona), Master, Instituto de Pesquisas Tecnológicas do Estado de São Paulo, São Paulo, 2015.
31 Harvard_Apparatus, "PHD 4400 Hpsi. High Force/High Pressure Programmable Syringe Pump," Harvard Apparatus.
32 Neto, B.B., Scarminio, I.S.,Bruns, R.E.: Como fazer experimentos, 4ta ed., Bookman, 2010.
33 Eliche, E.B.: Sistemas dispersos tópicos de lidocaína base en solución, PhD, Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Granada, Granada, 2010.
34 Thakral, S. Thakral, N.K.: Prediction of drug-polymer miscibility through the use of solubility parameter based flory-huggins interaction parameter and the experimental validation: PEG as model polymer, J. Pharm. Sci., 102, 2254 – 2263, (2013).
Copyright
Göller Verlag GmbH
