Synthesis and characterization of amphiphilic block copolymers by transesterification for nanoparticle production
Dias, André Rocha Monteiro; Miranda, Beatriz Nogueira Messias de; Cobas-Gomez, Houari; Poço, João Guilherme Rocha; Rubio, Mario Ricardo Gongora; Oliveira, Adriano Marim de
Abstract
Poly(ε-caprolactone)-block-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, triblock) and Poly(ε-caprolactone)-block-(poly(ethylene oxide)−poly(propylene oxide)−poly(ethylene oxide)-poly (ε-caprolactone) (PCL-PEO-PPO-PEO-PCL, pentablock) copolymers were synthesized by transesterification with reduction of PCL molecular mass, enabling fewer reactions, lower temperatures, and eliminating extensive purification steps. Free hydrophilic groups were removed from the samples by selective precipitation, and 1H-NMR, FTIR, GPC and DSC analyses characterized the structure and properties of the resulting copolymers. The detection of remaining hydrophilic groups indicates the formation of the amphiphilic block copolymers (BCPs). Further, we obtained polymeric nanoparticles with monodisperse size distribution profiles by nano-precipitation from both the triblock and the pentablock copolymers using a microfluidic device, resulting 144.6 and 188.9 nm size and 0.093 and 0.102 nm polydispersity index, respectively. The nanoparticle assembly depends on the copolymer composition, and the possibility of nanoparticle assembly corroborates to the block structure of the copolymers, and the success of this synthesis route to obtain BCPs.
Keywords
References
1 Lipinski, C. A. (2002). Poor aqueous solubility: an industry wide problem in drug discovery. American Pharmaceutical Review, 2(3), 82-85.
2 Lammers, T., Kiessling, F., Hennink, W. E., & Storm, G. (2011). Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. Journal of Controlled Release, 161(2), 175-187. http://dx.doi.org/10.1016/j.jconrel.2011.09.063. PMid:21945285.
3 Kabanov, A. V., Batrakova, E. V., & Alakhov, V. Y. (2002). Pluronic® block copolymers for overcoming drug resistance in cancer. Advanced Drug Delivery Reviews, 54(5), 759-779. http://dx.doi.org/10.1016/S0169-409X(02)00047-9. PMid:12204601.
4 Letchford, K., & Burt, H. (2007). A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes. European Journal of Pharmaceutics and Biopharmaceutics, 65(3), 259-269. http://dx.doi.org/10.1016/j.ejpb.2006.11.009. PMid:17196803.
5 Smart, T., Lomas, H., Massignani, M., Flores-Merino, M. V., Perez, L. R., & Battaglia, G. (2008). Block copolymer nanostructures. Nano Today, 3(3-4), 38-46. http://dx.doi.org/10.1016/S1748-0132(08)70043-4.
6 Bae, S. J., Suh, J. M., Sohn, Y. S., Bae, Y. H., Kim, S. W., & Jeong, B. (2005). Thermogelling Poly(caprolactone-b-ethylene glycol-b-caprolactone) Aqueous Solutions. Macromolecules, 38(12), 5260-5265. http://dx.doi.org/10.1021/ma050489m.
7 Lucke, A., Te, K., Schnell, E., Schmeer, G., & Go, A. (2000). Biodegradable poly(D,L-lactic acid)-poly(ethylene glycol)-monomethyl ether diblock copolymers: Structures and ether diblock copolymers: structures and surface properties relevant to their use as biomaterials. Biomaterials, 21(23), 2361-2370. http://dx.doi.org/10.1016/S0142-9612(00)00103-4. PMid:11055283.
8 Vila, A., Sanchez, A., Tobıo, M., Calvo, P., & Alonso, M. J. (2002). Design of biodegradable particles for protein delivery. Journal of Controlled Release, 78(1-3), 15-24. http://dx.doi.org/10.1016/S0168-3659(01)00486-2. PMid:11772445.
9 Meier, M. A. R., Aerts, S. N. H., Staal, B. B. P., Rasa, M., & Schubert, U. S. (2005). PEO-b-PCL block copolymers: Synthesis, detailed characterization, and selected micellar drug encapsulation behavior. Macromolecular Rapid Communications, 26(24), 1918-1924. http://dx.doi.org/10.1002/marc.200500591.
10 Sisson, A. L., Ekinci, D., & Lendlein, A. (2013). The contemporary role of ε -caprolactone chemistry to create advanced polymer architectures. Polymer, 54(17), 4333-4350. http://dx.doi.org/10.1016/j.polymer.2013.04.045.
11 Báez, J. E., Marcos-Fernández, Á., Lebrón-Aguilar, R., & Martínez-Richa, A. (2006). A novel route to α,ω-telechelic poly(ε-caprolactone) diols, precursors of biodegradable polyurethanes, using catalysis by decamolybdate anion. Polymer, 47(26), 8420-8429. http://dx.doi.org/10.1016/j.polymer.2006.10.023.
12 Cho, H. K., Cho, K. S., Cho, J. H., Choi, S. W., Kim, J. H., & Cheong, I. W. (2008). Synthesis and characterization of PEO-PCL-PEO triblock copolymers: Effects of the PCL chain length on the physical property of W1/O/W2 multiple emulsions. Colloids and Surfaces. B, Biointerfaces, 65(1), 61-68. http://dx.doi.org/10.1016/j.colsurfb.2008.02.017. PMid:18400473.
13 Gong, C. Y., Wu, Q. J., Dong, P. W., Shi, S., Fu, S. Z., Guo, G., Hu, H. Z., Zhao, X., Wei, Y. Q., & Qian, Z. Y (2009). Acute toxicity evaluation of biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PEG-PCL-PEG hydrogel. Journal of Biomedical Materials Research. Part B, Applied Biomaterials, 91(1), 26-36. http://dx.doi.org/10.1002/jbm.b.31370. PMid:19365823.
14 Hu, Y., Xie, J., Tong, Y. W., & Wang, C. H. (2007). Effect of PEG conformation and particle size on the cellular uptake efficiency of nanoparticles with the HepG2 cells. Journal of Controlled Release, 118(1), 7-17. http://dx.doi.org/10.1016/j.jconrel.2006.11.028. PMid:17241684.
15 Huang, Y., Gao, H., Gou, M., Ye, H., Liu, Y., Gao, Y., Peng, F., Qian, Z., Cen, X., & Zhao, Y. (2010). Acute toxicity and genotoxicity studies on poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) nanomaterials. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 696(2), 101-106. http://dx.doi.org/10.1016/j.mrgentox.2009.12.016. PMid:20060489.
16 Lu, F., Lei, L., Shen, Y. Y., Hou, J. W., Chen, W. L., Li, Y. G., & Guo, S. R. (2011). Effects of amphiphilic PCL-PEG-PCL copolymer addition on 5-fluorouracil release from biodegradable PCL films for stent application. International Journal of Pharmaceutics, 419(1-2), 77-84. http://dx.doi.org/10.1016/j.ijpharm.2011.07.020. PMid:21803141.
17 Ahmed, A., Wang, H., Yu, H., Zhou, Z. Y., Ding, Y., & Hu, Y. (2015). Surface engineered cyclodextrin embedded polymeric nanoparticles through host-guest interaction used for drug delivery. Chemical Engineering Science, 125, 121-128. http://dx.doi.org/10.1016/j.ces.2014.07.045.
18 Le Hellaye, M., Fortin, N., Guilloteau, J., Soum, A., Lecommandoux, S., & Guillaume, S. M. (2008). Biodegradable Polycarbonate- b -polypeptide and Polyester- b -polypeptide Block Copolymers: Synthesis and Nanoparticle Formation Towards Biomaterials. Biomacromolecules, 9(7), 1924-1933. http://dx.doi.org/10.1021/bm8001792. PMid:18529076.
19 Chen, C., Ke, J., Zhou, X. E., Yi, W., Brunzelle, J. S., Li, J., Yong, E. L., Xu, H. E., & Melcher, K. (2013). Structural basis for molecular recognition of folic acid by folate receptors. Nature, 500(7463), 486-489. http://dx.doi.org/10.1038/nature12327. PMid:23851396.
20 Gilson, P. R., Nebl, T., Vukcevic, D., Moritz, R. L., Sargeant, T., Speed, T. P., Schofield, L., & Crabb, B. S. (2006). Identification and stoichiometry of glycosylphosphatidylinositol-anchored membrane proteins of the human malaria parasite Plasmodium falciparum. Molecular & cellular proteomics, 5(7), 1286-1299. http://dx.doi.org/10.1074/mcp.M600035-MCP200. PMid:16603573.
21 Matsumura, S., Hlil, A. R., Lepiller, C., Gaudet, J., Guay, D., Shi, Z., Holdcroft, S., Hay, A. S. (2008). Ionomers for proton exchange membrane fuel cells with sulfonic acid groups on the end-groups: Novel branched poly(ether-ketone)s. Macromolecules, 49(1), 511-512.
22 Carrot, G., Hilborn, J. G., Trollsås, M., & Hedrick, J. L. (1999). Two general methods for the synthesis of thiol-functional polycaprolactones. Macromolecules, 32(16), 5264-5269. http://dx.doi.org/10.1021/ma990198b.
23 Guillaume, S. M., Schappacher, M., & Soum, A. (2003). Polymerization of ε-Caprolactone initiated by Nd(BH4)3(THF)3: Synthesis of hydroxytelechelic poly(ε-caprolactone). Macromolecules, 36(1), 54-60. http://dx.doi.org/10.1021/ma020993g.
24 Deng, X. M., & Hao, J. Y. (2001). Synthesis and characterization of poly(3-hydroxybutyrate) macromer of bacterial origin. European Polymer Journal, 37(1), 211-214. http://dx.doi.org/10.1016/S0014-3057(00)00090-2.
25 Špitalský, Z., Lacík, I., Lathová, E., Janigová, I., & Chodák, I. (2006). Controlled degradation of polyhydroxybutyrate via alcoholysis with ethylene glycol or glycerol. Polymer Degradation & Stability, 91(4), 856-861. http://dx.doi.org/10.1016/j.polymdegradstab.2005.06.019.
26 Impallomeni, G., Giuffrida, M., Barbuzzi, T., Musumarra, G., & Ballistreri, A. (2002). Acid catalyzed transesterification as a route to poly(3-hydroxybutyrate-co-ε-caprolactone) copolymers from their homopolymers. Biomacromolecules, 3(4), 835-840. http://dx.doi.org/10.1021/bm025525t. PMid:12099830.
27 Impallomeni, G., Carnemolla, G. M., Puzzo, G., Ballistreri, A., Martino, L., & Scandola, M. (2013). Characterization of biodegradable poly(3-hydroxybutyrate-co- butyleneadipate) copolymers obtained from their homopolymers by microwave-assisted transesterification. Polymer, 54(1), 65-74. http://dx.doi.org/10.1016/j.polymer.2012.11.030.
28 Montoro, S. R., Shigue, C. Y., Sordi, M. L. T., Santos, A. M., & Ré, M. I. (2010). Estudo cinético da redução da massa molar do poli(3-hidroxibutirato-co-3-hidroxivalerato) (PHBHV). Polímeros: Ciência e Tecnologia, 20(1), 19-24. http://dx.doi.org/10.1590/S0104-14282010005000005.
29 Zhou, S., Deng, X., & Yang, H. (2003). Biodegradable poly(ε-caprolactone)-poly(ethylene glycol) block copolymers: Characterization and their use as drug carriers for a controlled delivery system. Biomaterials, 24(20), 3563-3570. http://dx.doi.org/10.1016/S0142-9612(03)00207-2. PMid:12809785.
30 Zhou, Q., Zhang, Z., Chen, T., Guo, X., & Zhou, S. (2011). Preparation and characterization of thermosensitive pluronic F127-b-poly(e{open}-caprolactone) mixed micelles. Colloids and Surfaces. B, Biointerfaces, 86(1), 45-57. http://dx.doi.org/10.1016/j.colsurfb.2011.03.013. PMid:21489759.
31 Stainmesse, S., Orecchioni, A. M., Nakache, E., Puisieux, F., & Fessi, H. (1995). Formation and stabilization of a biodegradable polymeric colloidal suspension of nanoparticles. Colloid & Polymer Science, 273(5), 505-511. http://dx.doi.org/10.1007/BF00656896.
32 Chaudhuri, R. G., & Paria, S. (2012). Core/Shell Nanoparticles: classes, properties, synthesis mechanisms, characterization, and applications. Chemical Reviews, 112(4), 2373-2433. http://dx.doi.org/10.1021/cr100449n.
33 Ezhilarasi, P. N., Karthik, P., Chhanwal, N., & Anandharamakrishnan, C. (2013). Nanoencapsulation techniques for food bioactive components: a review. Food and Bioprocess Technology, 6(3), 628-647. http://dx.doi.org/10.1007/s11947-012-0944-0.
34 Chen, H., Khemtong, C., Yang, X., Chang, X., & Gao, J. (2011). Nanonization strategies for poorly water-soluble drugs. Drug Discovery Today, 16(7-8), 354-360. http://dx.doi.org/10.1016/j.drudis.2010.02.009. PMid:20206289. [
35 Chan, H. K., & Kwok, P. C. L. (2011). Production methods for nanodrug particles using the bottom-up approach. Advanced Drug Delivery Reviews, 63(6), 406-416. http://dx.doi.org/10.1016/j.addr.2011.03.011. PMid:21457742.
36 Nagavarma, B. V. N., Yadav, H. K. S., Ayaz, A., Vasudha, L. S., & Shivakumar, H. G. (2012). Different techniques for preparation of polymeric nanoparticles: a review. Journal of Pharmaceutical and Clinical Research, 5, 16-23.
37 Schubert, S. Jr, Delaney, J. T. Jr, & Schubert, U. S. (2011). Nanoprecipitation and nanoformulation of polymers: From history to powerful possibilities beyond poly(lactic acid). Soft Matter, 7(5), 1581-1888. http://dx.doi.org/10.1039/C0SM00862A.
38 LaMer, V. K., & Dinegar, R. H. (1950). Theory, production and mechanism of formation of monodispersed hydrosols. Journal of the American Chemical Society, 72(11), 4847-4854. http://dx.doi.org/10.1021/ja01167a001.
39 Cobas-Gomez, H., Gongora-Rubio, M. R., Agio, B. O., Novais Schianti, J., Kimura, V. T., Marim de Oliveira, A., Ramos, L. W. S. L. & Seabra, A. C. (2015). 3D Focalization microfluidic device built with LTCC technology for nanoparticle generation using nanoprecipitation route. Journal of Ceramic Science and Technology, 6(4), 329-338. http://dx.doi.org/10.4416/JCST2015-00062
40 Gongora-Rubio, M. R., Espinoza-Vallejos, P., Sola-Laguna, L., & Santiago-Avilés, J. J. (2001). Overview of low temperature co-Fired ceramics tape technology for meso-system technology (MsST). Sensors and Actuators. A, Physical, 89(3), 222-241. http://dx.doi.org/10.1016/S0924-4247(00)00554-9.
41 Cobas-Gomez, H. (2016). Sistemas microfluídicos cerâmicos para miniaturização de processos químicos aplicados à fabricação de nanopartículas (Master's thesis). Universidade de São Paulo, São Paulo.
42 Saghebasl, S., Davaran, S., Rahbarghazi, R., Montaseri, A., Salehi, R., & Ramazani, A. (2018). Synthesis and in vitro evaluation of thermosensitive hydrogel scaffolds based on (PNIPAAm-PCL-PEG-PCL-PNIPAAm)/Gelatin and (PCL-PEG-PCL)/Gelatin for use in cartilage tissue engineering. Journal of Biomaterials Science. Polymer Edition, 29(10), 1185-1206. http://dx.doi.org/10.1080/09205063.2018.1447627. PMid:29490569.
43 Zhu, Z., Xiong, C., Zhang, L., & Deng, X. (1997). Synthesis and characterization of poly (ε -caprolactone) - Poly (ethylene glycol) Block Copolymer. Journal of Polymer Science. Part A, Polymer Chemistry, 35(4), 709-714. http://dx.doi.org/10.1002/(SICI)1099-0518(199703)35:4<709::AID-POLA14>3.0.CO;2-R.
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