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decentered core-shell microcapsules in gravity and magnetic field Xue-Hui Ge, Jin-Pei Huang, Jian-Hong Xu*, Guang-Sheng Luo We developed a versatile and facile microfluidic method to form magnetic decentered core-shell microcapsule which is temperature-responsive to burst release directly toward target point.
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Controlled stimulation-burst targeted release by smart decentered core-shell microcapsules in gravity and magnetic field† Xue-Hui Ge, Jin-Pei Huang, Jian-Hong Xu*, Guang-Sheng Luo 5
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Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX DOI: 10.1039/b000000x By combining the gravity and magnetic force, we have developed a versatile and facile microfluidic method to form magnetic decentered core-shell microcapsules in which the directions of the oil core and the magnetic nanoparticles are opposite or same. When temperature rose above the LCST of the PNIPAm, the shell would shrink rapidly and the core would target burst release towards the contrary or same direction of the magnet. By adjusting the direction of the magnet, the release direction of active substance could be correspondingly controlled accurately. The stimulation-responsive microcapsules have considerable applications in drug delivery 1, agricultural industries 2 and medical technology 3, 4. They always united with the environment, taking advantage of pH5, temperature 6-8 ,ultrasound irradiation 9, magnetic fields 10 and electric field 11. Thus, PNIPAm was widely used with its excellent thermo-responsiveness. Drapala et al. 8 combined PNIPAm and glutathione to release protein encapsulated inside by controlling temperature above 37 ℃. However, the PNIPAm would remain in the release site after degradation which did harm to the tissue. Meanwhile, researchers have developed many ways to achieve controllable and accurate release, such as releasing from the surface 12, decomposition of the barrier by melting, swelling, degradation, or cracking 13 and by the block copolymer desorption in the shell 14. Recently, some researchers found that monodispersed drug barrier could maintain the uniformity and efficiency of drug dosage. Thus, microfluidics, whose advantages were high controlling in monodispersed emulsions 15 and wide application in protein crystallization 2, gene expression 16, biology 17, drug and gene delivery 3, has become promising methods recently 18-26. Weitz et al. 18 have applied the microfluidic device in the controlled particles release. Chu et al. 19-22 have achieved
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compound responsive microcapsules, such as thermo-responsive 20,21, and ion-recognizable microgels pH and temperature-responsive hydrogels 22, and by adding magnetic nanoparticles, these microgels became oriented 21. Kim et al. 23 have formed double emulsions with hydrogen network and released dextran and BSA in a controlled pace. By using polymeric membrane, DiLauro et al. 24 and Abbaspourrad et al. 25 achieved a tunable rates of release. Furthermore, by adjusting the PAA-b-PMMA content of the shell, the release rate could be controlled 26. These methods could achieve controllable release; however, they failed to achieve orientated release. In the last few years, some researchers have utilized asymmetrical morphology 27-31 to enhance orientation. For instance, Chen et al. 27 utilized the branched polymers to form Janus microbeads under thermo-and magnetic field. Jeong et al.28 employed the phase separation to prepare magnetic Janus particles. These ways offered orientation property by synthesizing Janus microgels with magnetic nanoparticles. However, these methods still lacked accuracy and efficiency because they only release the actives in a certain area, then the actives reached their targets by mass transfer. Here we report a novel and facile microfluidic approach to achieve an accurate and efficient targeted release method of the active substance in the core by utilizing the asymmetric advantage and magnetic ability of magnetic decentered core-shell microcapsules. The microcapsules could burst out the drugs directly toward the target, targeting the tissue or cells efficiently. The synthesis process of these microcapsules was shown in Schematic 1.
The State Key Lab of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China. E-mail: [email protected] . Tel: +86-10-62773017. Fax: +86-10-62773017. † Electronic Supplementary Information (ESI) available: Fig. S1-S4 (The preparation experiment conditions and the control of double emulsions with different inner core size and shell sizet); Movies S1-S6 (Encapsulation, the rotating movement under magnetic, the burst release of decentered core-shell microcapsules with the core in the contrary and same direction of the magnetic force). See DOI: 10.1039/b000000x/
This journal is © The Royal Society of Chemistry 2014
Schematic 1. The synthesis process of magnetic decentered core-shell microcapsules. [journal], [year], [vol], 00–00
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Published on 01 September 2014. Downloaded by University of California - San Diego on 14/09/2014 14:04:24.
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Firstly, we used the microfluidic device as Fig. S1 to synthesize the magnetic core-shell O/W/O double emulsions. The inner and outer phases were soybean oil and the middle phase was NIPAm aqueous solution with 1.0 wt.‰ magnetic nanoparticles. The chemical materials and the device details could be found in ESI† . Then we collected the emulsions in the outer phase ambient and solidify them under magnetic and gravitational fields with UV light for about 100s in icy bath, thus magnetic decentered core-shell microcapsules were obtained.
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location of magnet at the left or bottom of the microcapsule. As the ambient temperature increased, the microcapsule shrank View Article Online 10.1039/C4LC00645C immediately and burst releases the actives DOI: directly towards the targets. By breaking down the high-speed video, we observed the five stages in the burst release of the microcapsule. Firstly, the decentered core-shell microcapsule was the original stage. Secondly, in extruding stage, the microcapsule started to shrink when the temperature increased. The thicker side of shell shrank faster than the thinner side, pushing the inner core even more eccentric. Then, coming to deforming stage, the difference of shrinkage forces enlarged the difference of the shell thickness, deforming the inner core. When deforming enlarges, the thinnest side of shell started rupture, the shrinkage force arrived to the maximum, so it was rupture stage. Finally, it went to burst release stage, in which the inner core burst out directly with a high speed and a straight ejection trace opposite to the magnet. The five stages are: 1-original stage; 2-extuding stage; 3-deforming stage; 4-rupture stage and 5-burst release. The transformation of stages is less than 10s.
Fig. 1 Microphotographs of monodispersed core-shell double emulsions and the solidification process under gravitational and magnetic fields. The black dots in Fig. 1b represents iron nanoparticles, they started aggregating under magnetic force while the inner core floated up. Then the nanoparticles aggregated down as shown in Fig. 1c and Fig. 1e. The microcapsule after solidification is shown in Fig. 1f. The UV exposure time was 100s. The bars represent 250 μm. Fig. 1 depicted the monodispersed emulsions, their size range and the solidification process. The CVs of size of our emulsions were less than 5% and the size of inner cores could be adjusted from 150 μm to 340 μm by changing flow rates. More information about the size and the number of inner cores could be found in supporting information (see ESI† Fig. S2&S3). During solidification process, the magnetic nanoparticles aggregated down under down-faced magnetic force and the inner soybean core floated because of lighter density under gravity. According to pre-experiment, we found that 100s UV exposure were the appropriate time to obtain the transparent (easy for later release observation) magnetic decentered core-shell microcapsules (For details about pre-experiment, see ESI† Fig. S4). Fig. 1b-f demonstrates the process of solidification under magnetic and gravitational force. To depict the magnetic microcapsules oriented movement under magnet, we rotated the microcapsules by rotating magnet. The controlled movement process was shown in the supporting information (see ESI† movie S2). In our experiments, the solidification process was operated under LCST by putting the collect dish in the ice-water bath. After separating the microcapsules to water phase, we loaded the swelling microcapsules in a tube with sealed end and two pipelines to import and export water. By replacing cold water with hot water, we made the ambient temperature rise from 25℃ to 60℃ in 10 seconds and took videos all through the burst release process. The microphotographs and the corresponding schematic diagram of targeted release process were shown in Fig. 2. Fig. 2a & 2b were the top view and the side view of two typical burst release processes. The burst release processes videos could be found in the supporting information (see ESI† movie S3 and movie S4). The bust release direction could be controlled towards right (Fig. 2a) or towards up (Fig. 2b) simply by changing the 2
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Fig.2 The process of burst release with controlled direction. Fig. 2a and Fig. 2b are the top view and the side view of the targeted burst release process. The magnet in Fig 2a is on the left while in Fig 2b is in the bottom of microcapsule and the arrows showing the burst releasing direction were towards right and up respectively, on contrary of the magnetic force. These micrographs depicted the five stage transformation of targeted burst release in less than 10s. The five stages are: 1-original stage; 2-extuding stage; 3-deforming stage; 4-rupture stage and 5-burst release. The black bars represent 200 μm. This approach of the targeted burst release with accurate control could be applied in wider applications for its simplicity and scalability. We could obtain different direction relationship between active substance and the magnetic nanoparticles by changing the adding location of magnetic nanoparticles. Fig. 3 This journal is © The Royal Society of Chemistry [year]
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In summary, we developed a novel and simple microfluidic approach to achieve targeted burst release with good control in releasing location and direction by preparing magnetic decentered core-shell microcapsules. The temperature-responsive nature of PNIPAm microcapsule with asymmetric distribution of the shell thickness contributes the asymmetric shrinkage of shell, thus realizing the burst release of active substance towards the thinner shell membrane direction. This direction could be accurately controlled by introducing the iron dioxide magnetic nanoparticles into different phase. This method, with accurate targeting and facile controlling abilities, offers a novel approach to control stimuli-responsive targeted release of active substance. Furthermore, these microcapsules combing two or more environmental responses and asymmetric structures can greatly contribute to the development of barrier synthesis with highly-tailored drug release. This journal is © The Royal Society of Chemistry 2014
The authors gratefully acknowledge the supports DOI: 10.1039/C4LC00645C of the National Natural Science Foundation of China (21322604, 21136006, 21036002) , National Basic Research Program of China (2012CBA01203) and A Foundation for the Author of National Excellent Doctoral Dissertation of PR China (FANEDD 201053).
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Fig. 3 The diagram and microphotographs showing the solidification and burst release processes of the microcapsules in which the nanoparticles dispersed in the oil core. Fig. 3a is the schematic diagram of the formation process. The magnetic nanoparticles are dispersed in the inner oil and other steps were the same with Scheme1. Fig. 3b shows the micrographs of the double emulsion, the microcapsule and the top view of microcapsule to see the magnetic nanoparticles in the core. Fig. 3c shows the down-faced burst release process of inner cores in less than 10s. The magnet is in the bottom. The black bars represent 200 μm.
ACKNOWLEDGMENT
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C. X. Zhao, Adv. Drug Deliver. Rev., 2013, 65, 1420-1446. K. Zhang, Q. Liang, S. Ma, X. Mu, P. Hu, Y. Wang and G. Luo, Lab Chip., 2009, 9, 2992-2999. 3. Y. H. Lin, H. F. Liang, C. K. Chung, M. C. Chen and H. W. Sung, Biomaterials, 2005, 26, 2105-2113. 4. J. H. Xu, H. Zhao, W. J. Lan and G. S. Luo, Adv. Healthc. Mater., 2012, 1, 106-111. 5. W. Khan, J. H. Choi, G. M. Kim and S. Y. Park, Lab Chip., 2011, 11, 3493-3498. 6. W. Wei, J. Du, M. Yan, Z. Hu and Y. Lu, J. Control. Release., 2013, 172, e115-116. 7. M. Jalaal and B. Stoeber, Soft Matter, 2014, 10, 808-812. 8. P. W. Drapala, B. Jiang, Y. C. Chiu, W. F. Mieler, E. M. Brey, J. J. Kang-Mieler and V. H. Perez-Luna, Pharm. Res., 2014, 31, 742-753. 9. L.Kromidas, E.Perrier,J. Flanagan,R.Rivero, I. Bonnet, Int. J.Cosmet. Sci. 2006, 28, 103–108. 10. S. H. Hu, C. H. Tsai, C. F. Liao, D. M. Liu, S. Y. Chen,Langmuir 2008, 24, 11811–11818. 11. D. G. Shchukin, D. O. Grigoriev, H. Mohwald, Soft Matter,2010, 6, 720–725. 12. Q. Xu, M. Hashimoto, T. T. Dang, T. Hoare, D. S. Kohane, G. M. Whitesides, R. Langer and D. G. Anderson, Small, 2009, 5, 1575-1581. 13. A. P. Esser-Kahn, S. A. Odom, N. R. Sottos, S. R. White and J. S. Moore, Macromol., 2011, 44, 5539-5553. 14. S. B. Zhou, J. Fan, S. S. Datta, M. Guo, X. Guo and D. A. Weitz, Adv. Func.tMater., 2013, 23, 5925-5929. 15. J.-H. Xu, X.-H. Ge, R. Chen and G.-S. Luo, RSC Adv. 2014, 4, 1900-1906. 16. J.-u. Shim, L. F. Olguin, G. Whyte, D. Scott, A. Babtie, C. Abell, W. T. S. Huck and F. Hollfelder, J. Am. Chem. Soc., 2009, 131, 15251-15256. 17. Y. Schaerli and F. Hollfelder, Mol. BioSyst., 2009, 5, 1392-1404. 18. W. J. Duncanson, T. Lin, A. R. Abate, S. Seiffert, R. K. Shah and D. A. Weitz, Lab Chip., 2012, 12, 2135-2145. 19. Y.C.Chen, R.Xie, L.Y.Chu, J. Membr. Sci., 2013, 442, 206-215. 20. X.J.Ju, L.Liu, R.Xie, C. H. Niu and L.Y.Chu, Polym., 2009, 50, 922-929. 21. W. Wang, L. Liu, X. J. Ju, D. Zerrouki, R. Xie,L.H. Yang and L.Y. Chu, Chem. Phys. Chem, 2009, 10, 2405-2409. 22. J.Zhang, R,Xie, S.B.Zhang, C.J. Cheng, X.J.Ju and L.Y.Chu, Polym., 2009, 50, 2516-2525. 23. K. Shin-Hyun, K. Jin Woong, K. Do-Hoon, H. Sang-Hoon and D. A. Weitz, Small, 2013, 9, 124-131. 24. A. M. DiLauro, A. Abbaspourrad, D. A. Weitz and S. T. Phillips, Macromol., 2013, 46, 3309-3313. 25. A. Abbaspourrad, N. J. Carroll, S. H. Kim and D. A. Weitz, J. Am. Chem. Soc. 2013, 135, 7744-7750. 26. A. Abbaspourrad, S. S. Datta and D. A. Weitz, Langmuir, 2013, 29, 12697-12702. 27. Y. Chen, G. Nurumbetov, R. Chen, N. Ballard and S. A. Bon, Langmuir, 2013, 29, 12657-12662J.28. 28. Jeong, E. Um, J.-K. Park and M. W. Kim, RSC Adv., 2013, 3, 11801.29. 29. B. Liu, J. G. Liu, F. X. Liang, Q. Wang, C. L. Zhang, X. Z. Qu, J. L. Li, D. Qiu and Z. Z. Yang, Macromol., 2012, 45, 5176-5184. 30. H.Rezvantalab and S. Shojaei-Zadeh, Soft Matter, 2013, 9, 3640-3650. 31. Y. Zhang, H. R. Liu and F. W. Wang, Colloid Polym. Sci., 2013, 291, 2993-3003.
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shows the formation and the inner core release process of microcapsules in which the nanoparticles are dispersed in the core. To prove the magnetic nanoparticles were in the core, we compared the behaviours between two microcapsules: one had the core within nanoparticles, the other one’s core was removed. Under the upside magnet force, the one with the magnetic core moved up while the other stayed still. The result showed that the magnetic nanoparticles were successfully encapsulated in the core. This movie could be found in the supporting information (see ESI† movie S5). Thus, the core faced down under the down-faced magnetic force and burst release downside. The process could also be divided into five stages as the above process. The release process movie could be found in supporting information (see ESI† movie S6).Thus the burst release direction could be the converse or the same to the directional magnetic force.
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Lab on a Chip Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: X. Ge, J. Huang, J. Xu and G. Luo, Lab Chip, 2014, DOI: 10.1039/C4LC00645C.
This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains.
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decentered core-shell microcapsules in gravity and magnetic field Xue-Hui Ge, Jin-Pei Huang, Jian-Hong Xu*, Guang-Sheng Luo We developed a versatile and facile microfluidic method to form magnetic decentered core-shell microcapsule which is temperature-responsive to burst release directly toward target point.
Lab on a Chip Accepted Manuscript
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Controlled stimulation-burst targeted release by smart
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Controlled stimulation-burst targeted release by smart decentered core-shell microcapsules in gravity and magnetic field† Xue-Hui Ge, Jin-Pei Huang, Jian-Hong Xu*, Guang-Sheng Luo 5
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Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX DOI: 10.1039/b000000x By combining the gravity and magnetic force, we have developed a versatile and facile microfluidic method to form magnetic decentered core-shell microcapsules in which the directions of the oil core and the magnetic nanoparticles are opposite or same. When temperature rose above the LCST of the PNIPAm, the shell would shrink rapidly and the core would target burst release towards the contrary or same direction of the magnet. By adjusting the direction of the magnet, the release direction of active substance could be correspondingly controlled accurately. The stimulation-responsive microcapsules have considerable applications in drug delivery 1, agricultural industries 2 and medical technology 3, 4. They always united with the environment, taking advantage of pH5, temperature 6-8 ,ultrasound irradiation 9, magnetic fields 10 and electric field 11. Thus, PNIPAm was widely used with its excellent thermo-responsiveness. Drapala et al. 8 combined PNIPAm and glutathione to release protein encapsulated inside by controlling temperature above 37 ℃. However, the PNIPAm would remain in the release site after degradation which did harm to the tissue. Meanwhile, researchers have developed many ways to achieve controllable and accurate release, such as releasing from the surface 12, decomposition of the barrier by melting, swelling, degradation, or cracking 13 and by the block copolymer desorption in the shell 14. Recently, some researchers found that monodispersed drug barrier could maintain the uniformity and efficiency of drug dosage. Thus, microfluidics, whose advantages were high controlling in monodispersed emulsions 15 and wide application in protein crystallization 2, gene expression 16, biology 17, drug and gene delivery 3, has become promising methods recently 18-26. Weitz et al. 18 have applied the microfluidic device in the controlled particles release. Chu et al. 19-22 have achieved
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compound responsive microcapsules, such as thermo-responsive 20,21, and ion-recognizable microgels pH and temperature-responsive hydrogels 22, and by adding magnetic nanoparticles, these microgels became oriented 21. Kim et al. 23 have formed double emulsions with hydrogen network and released dextran and BSA in a controlled pace. By using polymeric membrane, DiLauro et al. 24 and Abbaspourrad et al. 25 achieved a tunable rates of release. Furthermore, by adjusting the PAA-b-PMMA content of the shell, the release rate could be controlled 26. These methods could achieve controllable release; however, they failed to achieve orientated release. In the last few years, some researchers have utilized asymmetrical morphology 27-31 to enhance orientation. For instance, Chen et al. 27 utilized the branched polymers to form Janus microbeads under thermo-and magnetic field. Jeong et al.28 employed the phase separation to prepare magnetic Janus particles. These ways offered orientation property by synthesizing Janus microgels with magnetic nanoparticles. However, these methods still lacked accuracy and efficiency because they only release the actives in a certain area, then the actives reached their targets by mass transfer. Here we report a novel and facile microfluidic approach to achieve an accurate and efficient targeted release method of the active substance in the core by utilizing the asymmetric advantage and magnetic ability of magnetic decentered core-shell microcapsules. The microcapsules could burst out the drugs directly toward the target, targeting the tissue or cells efficiently. The synthesis process of these microcapsules was shown in Schematic 1.
The State Key Lab of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China. E-mail: [email protected] . Tel: +86-10-62773017. Fax: +86-10-62773017. † Electronic Supplementary Information (ESI) available: Fig. S1-S4 (The preparation experiment conditions and the control of double emulsions with different inner core size and shell sizet); Movies S1-S6 (Encapsulation, the rotating movement under magnetic, the burst release of decentered core-shell microcapsules with the core in the contrary and same direction of the magnetic force). See DOI: 10.1039/b000000x/
This journal is © The Royal Society of Chemistry 2014
Schematic 1. The synthesis process of magnetic decentered core-shell microcapsules. [journal], [year], [vol], 00–00
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Lab on a Chip Accepted Manuscript
Published on 01 September 2014. Downloaded by University of California - San Diego on 14/09/2014 14:04:24.
www.rsc.org/xxxxxx
Published on 01 September 2014. Downloaded by University of California - San Diego on 14/09/2014 14:04:24.
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Firstly, we used the microfluidic device as Fig. S1 to synthesize the magnetic core-shell O/W/O double emulsions. The inner and outer phases were soybean oil and the middle phase was NIPAm aqueous solution with 1.0 wt.‰ magnetic nanoparticles. The chemical materials and the device details could be found in ESI† . Then we collected the emulsions in the outer phase ambient and solidify them under magnetic and gravitational fields with UV light for about 100s in icy bath, thus magnetic decentered core-shell microcapsules were obtained.
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location of magnet at the left or bottom of the microcapsule. As the ambient temperature increased, the microcapsule shrank View Article Online 10.1039/C4LC00645C immediately and burst releases the actives DOI: directly towards the targets. By breaking down the high-speed video, we observed the five stages in the burst release of the microcapsule. Firstly, the decentered core-shell microcapsule was the original stage. Secondly, in extruding stage, the microcapsule started to shrink when the temperature increased. The thicker side of shell shrank faster than the thinner side, pushing the inner core even more eccentric. Then, coming to deforming stage, the difference of shrinkage forces enlarged the difference of the shell thickness, deforming the inner core. When deforming enlarges, the thinnest side of shell started rupture, the shrinkage force arrived to the maximum, so it was rupture stage. Finally, it went to burst release stage, in which the inner core burst out directly with a high speed and a straight ejection trace opposite to the magnet. The five stages are: 1-original stage; 2-extuding stage; 3-deforming stage; 4-rupture stage and 5-burst release. The transformation of stages is less than 10s.
Fig. 1 Microphotographs of monodispersed core-shell double emulsions and the solidification process under gravitational and magnetic fields. The black dots in Fig. 1b represents iron nanoparticles, they started aggregating under magnetic force while the inner core floated up. Then the nanoparticles aggregated down as shown in Fig. 1c and Fig. 1e. The microcapsule after solidification is shown in Fig. 1f. The UV exposure time was 100s. The bars represent 250 μm. Fig. 1 depicted the monodispersed emulsions, their size range and the solidification process. The CVs of size of our emulsions were less than 5% and the size of inner cores could be adjusted from 150 μm to 340 μm by changing flow rates. More information about the size and the number of inner cores could be found in supporting information (see ESI† Fig. S2&S3). During solidification process, the magnetic nanoparticles aggregated down under down-faced magnetic force and the inner soybean core floated because of lighter density under gravity. According to pre-experiment, we found that 100s UV exposure were the appropriate time to obtain the transparent (easy for later release observation) magnetic decentered core-shell microcapsules (For details about pre-experiment, see ESI† Fig. S4). Fig. 1b-f demonstrates the process of solidification under magnetic and gravitational force. To depict the magnetic microcapsules oriented movement under magnet, we rotated the microcapsules by rotating magnet. The controlled movement process was shown in the supporting information (see ESI† movie S2). In our experiments, the solidification process was operated under LCST by putting the collect dish in the ice-water bath. After separating the microcapsules to water phase, we loaded the swelling microcapsules in a tube with sealed end and two pipelines to import and export water. By replacing cold water with hot water, we made the ambient temperature rise from 25℃ to 60℃ in 10 seconds and took videos all through the burst release process. The microphotographs and the corresponding schematic diagram of targeted release process were shown in Fig. 2. Fig. 2a & 2b were the top view and the side view of two typical burst release processes. The burst release processes videos could be found in the supporting information (see ESI† movie S3 and movie S4). The bust release direction could be controlled towards right (Fig. 2a) or towards up (Fig. 2b) simply by changing the 2
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Fig.2 The process of burst release with controlled direction. Fig. 2a and Fig. 2b are the top view and the side view of the targeted burst release process. The magnet in Fig 2a is on the left while in Fig 2b is in the bottom of microcapsule and the arrows showing the burst releasing direction were towards right and up respectively, on contrary of the magnetic force. These micrographs depicted the five stage transformation of targeted burst release in less than 10s. The five stages are: 1-original stage; 2-extuding stage; 3-deforming stage; 4-rupture stage and 5-burst release. The black bars represent 200 μm. This approach of the targeted burst release with accurate control could be applied in wider applications for its simplicity and scalability. We could obtain different direction relationship between active substance and the magnetic nanoparticles by changing the adding location of magnetic nanoparticles. Fig. 3 This journal is © The Royal Society of Chemistry [year]
Lab on a Chip Accepted Manuscript
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In summary, we developed a novel and simple microfluidic approach to achieve targeted burst release with good control in releasing location and direction by preparing magnetic decentered core-shell microcapsules. The temperature-responsive nature of PNIPAm microcapsule with asymmetric distribution of the shell thickness contributes the asymmetric shrinkage of shell, thus realizing the burst release of active substance towards the thinner shell membrane direction. This direction could be accurately controlled by introducing the iron dioxide magnetic nanoparticles into different phase. This method, with accurate targeting and facile controlling abilities, offers a novel approach to control stimuli-responsive targeted release of active substance. Furthermore, these microcapsules combing two or more environmental responses and asymmetric structures can greatly contribute to the development of barrier synthesis with highly-tailored drug release. This journal is © The Royal Society of Chemistry 2014
The authors gratefully acknowledge the supports DOI: 10.1039/C4LC00645C of the National Natural Science Foundation of China (21322604, 21136006, 21036002) , National Basic Research Program of China (2012CBA01203) and A Foundation for the Author of National Excellent Doctoral Dissertation of PR China (FANEDD 201053).
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Fig. 3 The diagram and microphotographs showing the solidification and burst release processes of the microcapsules in which the nanoparticles dispersed in the oil core. Fig. 3a is the schematic diagram of the formation process. The magnetic nanoparticles are dispersed in the inner oil and other steps were the same with Scheme1. Fig. 3b shows the micrographs of the double emulsion, the microcapsule and the top view of microcapsule to see the magnetic nanoparticles in the core. Fig. 3c shows the down-faced burst release process of inner cores in less than 10s. The magnet is in the bottom. The black bars represent 200 μm.
ACKNOWLEDGMENT
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Lab on a Chip Accepted Manuscript
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shows the formation and the inner core release process of microcapsules in which the nanoparticles are dispersed in the core. To prove the magnetic nanoparticles were in the core, we compared the behaviours between two microcapsules: one had the core within nanoparticles, the other one’s core was removed. Under the upside magnet force, the one with the magnetic core moved up while the other stayed still. The result showed that the magnetic nanoparticles were successfully encapsulated in the core. This movie could be found in the supporting information (see ESI† movie S5). Thus, the core faced down under the down-faced magnetic force and burst release downside. The process could also be divided into five stages as the above process. The release process movie could be found in supporting information (see ESI† movie S6).Thus the burst release direction could be the converse or the same to the directional magnetic force.
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