Experimental study of manufacturing and characterization of a flow-focusing microchannel to produce thermoresponsive microparticles for on-demand smart drug delivery

Document Type : Research Article

Authors

Shahrood University of Technology

Abstract

In targeted drug delivery, the use of temperature-sensitive micro-drops as drug carriers has recently been considered. In this approach, the use of N-isopropylacrylamide microparticles as temperature-sensitive drug carriers can be effective in the topical treatment of chronic burn wounds and diabetes. In this study, first, a flow-focusing microchannel was fabricated by photolithography. Then N-isopropylacrylamide polymer solution was made with different percentages and used as a drop phase in the microchannel. 10% N-isopropylacrylamide solutions and silicone oil were used as intermediate and continuous phase currents, respectively, and N-isopropylacrylamide microparticles were produced by microchannel. The results of the study showed that by changing the ratio of intermittent to continuous phase flow from 0.14 to 0.84, the diameter of the produced droplets increases from 360 to 515 microns. It was also observed that if the syringe container containing the polymer fluid is kept cold, an aqueous solution containing 10% N-isopropylacrylamide, 0.3% BIS and 4% ammonium persulfate can be used as the drop phase And thus produced temperature-sensitive polymer droplets. Increasing the temperature of the produced micro-drops from 20 to 26° C led to a 50% reduction in their diameter.

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[1] M. Sponchioni, U.C. Palmiero, D. Moscatelli, Thermo-responsive polymers: Applications of smart materials in drug delivery and tissue engineering, Materials Science and Engineering: C, 102 (2019) 7.
[2] A. Gandhi, A. Paul, S.O. Sen, K.K. Sen, Studies on thermoresponsive polymers: Phase behaviour, drug delivery and biomedical applications, asian journal of pharmaceutical sciences, 10(2) (2015) 99-107.
[3] F. Zhang, W. Wu, X. Zhang, X. Meng, G. Tong, Y. Deng, Temperature-sensitive poly-NIPAm modified cellulose nanofibril cryogel microspheres for controlled drug release, Cellulose, 23(1) (2016) 415-425.
[4] R.R. Kokardekar, V.K. Shah, H.R. Mody, PNIPAM Poly (N-isopropylacrylamide): A thermoresponsive “smart” polymer in novel drug delivery systems, Internet Journal of Medical Update-EJOURNAL, 7(2) (2012).
[5] F. Natalia, G. Stoychev, N. Puretskiy, I. Leonid, V. Dmitry, Porous thermo-responsive pNIPAM microgels, European Polymer Journal, 68 (2015) 650-656.
[6] A. Burmistrova, M. Richter, C. Uzum, R.v. Klitzing, Effect of cross-linker density of P (NIPAM-co-AAc) microgels at solid surfaces on the swelling/shrinking behaviour and the Young’s modulus, Colloid and Polymer Science, 289(5-6) (2011) 613-624.
[7] K. Jain, R. Vedarajan, M. Watanabe, M. Ishikiriyama, N. Matsumi, Tunable LCST behavior of poly (N-isopropylacrylamide/ionic liquid) copolymers, Polymer Chemistry, 6(38) (2015) 6819-6825.
[8] A. Burmistrova, M. Richter, M. Eisele, C. Üzüm, R. Von Klitzing, The effect of co-monomer content on the swelling/shrinking and mechanical behaviour of individually adsorbed PNIPAM microgel particles, Polymers, 3(4) (2011) 1575-1590.
[9] E. Roux, R. Stomp, S. Giasson, M. PÉzolet, P. Moreau, J.C. Leroux, Steric stabilization of liposomes by pH‐responsive N‐isopropylacrylamide copolymer, Journal of pharmaceutical sciences, 91(8) (2002) 1795-1802.
[10] H. Hathaway, D.R. Alves, J. Bean, P.P. Esteban, K. Ouadi, J.M. Sutton, A.T.A. Jenkins, Poly (N-isopropylacrylamide-co-allylamine)(PNIPAM-co-ALA) nanospheres for the thermally triggered release of Bacteriophage K, European Journal of Pharmaceutics and Biopharmaceutics, 96 (2015) 437-441.
[11] S. Bagherifard, A. Tamayol, P. Mostafalu, M. Akbari, M. Comotto, N. Annabi, M. Ghaderi, S. Sonkusale, M.R. Dokmeci, A. Khademhosseini, Dermal patch with integrated flexible heater for on demand drug delivery, Advanced healthcare materials, 5(1) (2016) 175-184.
[12] B. Behm, P. Babilas, M. Landthaler, S. Schreml, Cytokines, chemokines and growth factors in wound healing, Journal of the European Academy of Dermatology and Venereology, 26(7) (2012) 812-820.
[13] R.D. Galiano, O.M. Tepper, C.R. Pelo, K.A. Bhatt, M. Callaghan, N. Bastidas, S. Bunting, H.G. Steinmetz, G.C. Gurtner, Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells, The American journal of pathology, 164(6) (2004) 1935-1947.
[14] M.R. Prausnitz, R. Langer, Transdermal drug delivery, Nature biotechnology, 26(11) (2008) 1261.
[15] T.F. Tadros, Fundamental principles of emulsion rheology and their applications, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 91 (1994) 39-55.
[16] S. Takeuchi, P. Garstecki, D.B. Weibel, G.M. Whitesides, An axisymmetric flow‐focusing microfluidic device, Advanced materials, 17(8) (2005) 1067-1072.
[17] Y.-C. Tan, J.S. Fisher, A.I. Lee, V. Cristini, A.P. Lee, Design of microfluidic channel geometries for the control of droplet volume, chemical concentration, and sorting, Lab on a Chip, 4(4) (2004) 292-298.
[18] E.R. Lee, Microdrop generation, CRC press, 2018.
[19] L. Martín‐Banderas, M. Flores‐Mosquera, P. Riesco‐Chueca, A. Rodríguez‐Gil, Á. Cebolla, S. Chávez, A.M. Gañán‐Calvo, Flow focusing: a versatile technology to produce size‐controlled and specific‐morphology microparticles, Small, 1(7) (2005) 688-692.