Encapsulación de hemoglobina en micropartículas a base de ovoproteínas y carragenano, generadas por microfluídica: retención y liberación de hierro y evaluación in vitro
DOI:
https://doi.org/10.24215/30089336e015Palabras clave:
micropartículas, encapsulación, liberación controlada, hierro hemínico, tecnología microfluídicaResumen
Este trabajo evalúa el uso de tecnología microfluídica para la encapsulación de hemoglobina bovina en polvo como fuente de hierro hemínico, con el objetivo de mejorar estrategias de suplementación. Para la generación de micropartículas se utilizó un dispositivo microfluídico con juntura en cruz, empleando aceite de oliva como fase continua y una mezcla de clara de huevo/κ-carragenato en solución como fase dispersa. Las microgotas se irradiaron con microondas (900 W de potencia, 15 s). Las micropartículas obtenidas presentaron morfología esférica y su distribución de tamaño resultó monodispersa, con un diámetro promedio de 203 µm. El sistema mostró una adecuada retención de hierro, sin detectarse migración hacia la fase continua. La liberación in vitro en condiciones simuladas de pH gastrointestinal alcanzó aproximadamente un 24 % a las 72 h, con un mecanismo controlado por difusión. Los ensayos de citotoxicidad en células Caco-2 indicaron ausencia de efectos adversos, con una viabilidad cercana al 100 %. Los estudios de permeabilidad mostraron que alrededor del 11.6 % del hierro liberado atravesó la monocapa celular. Estos resultados evidencian la viabilidad de sistemas microfluídicos para la administración de hierro hemínico, aunque se requiere optimización para mejorar su liberación y permeabilidad in vitro.
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Referencias
Abecia, L., McCartney, A. L. y Klinder, A. (12-13 de mayo de 2009). Efecto de los productos de fermentación del triptófano en la resistencia eléctrica transepitelial en un modelo in vitro de colon [trabajo completo]. XXXIX Jornadas de Estudio y XIII Jornadas sobre producción animal. Asociación Interprofesional para el Desarrollo Agrario, Zaragoza. España.
Ahmed, H., Khan, E. A. y Stokke, B. T. (2023). Microfluidic dual picoinjection based encapsulation of hemoglobin in alginate microcapsules reinforced by a poly(L-lysine)-g-poly(ethylene glycol). Soft Matter, 19(1), 69-79. https://doi.org/10.1039/d2sm01045c
Bailey, R. L., West Jr., K. P. y Black, R. E. (2015). The epidemiology of global micronutrient deficiencies. Annals of Nutrition and Metabolism, 66(2), 22-33. https://doi.org/10.1159/000371618
Bamshad, A., Nikfarjam, A. y Khaleghi, H. (2016). A new simple and fast thermally-solvent assisted method to bond PMMA-PMMA in micro-fluidics devices. Journal of Micromechanics and Microengineering, 26(6), 065017. http://iopscience.iop.org/0960-1317/26/6/065017
Benson, A. E., Shatzel, J. J., Ryan, K. S., Hedges, M. A., Martens, K., Aslan, J. E. y Lo, J. O. (2022). The incidence, complications, and treatment of iron deficiency in pregnancy. European Journal of Haematology, 109(6), 633-642. https://doi.org/10.1111/ejh.13870
Buzala, M., Slomka, A. y Janicki, B. (2016). Heme iron in meat as the main source of iron in the human diet. Journal of Elementology, 21(1), 303-314. https://doi.org/10.5601/jelem.2015.20.1.850
Cano-Sancho, G., González-Arias, C. A., Ramos, A. J., Sanchis, V. y Fernández-Cruz, M. L. (2015). Cytotoxicity of the mycotoxins deoxynivalenol and ochratoxin A on Caco-2 cell line in presence of resveratrol. Toxicology in Vitro, 29(7), 1639-1646. http://dx.doi.org/10.1016/j.tiv.2015.06.020
Choi, A., Seo, K. D., Kim, D. W., Kim, B. C. y Kim, D. S. (2017). Recent advances in engineering microparticles and their nascent utilization in biomedical delivery and diagnostic applications. Lab Chip, 17(4), 591-613. https://doi.org/10.1039/c6lc01023g
Churio, O., Pizarro, F. y Valenzuela, C. (2018). Preparation and characterization of iron-alginate beads with some types of iron used in supplementation and fortification strategies. Food Hydrocolloids, 74, 1-10. http://doi.org/10.1016/j.foodhyd.2017.07.020
Culeddu, G., Su, L., Cheng, Y., Pereira, D. I. A., Payne, R. A., Powell, J. J. y Hughes, D. A. (2022). Novel oral iron therapy for iron deficiency anaemia: How to value safety in a new drug? British Journal of Clinical Pharmacology, 88(3), 1347-1357. https://doi.org/10.1111/bcp.15078
Domellöf, M., Braegger, C., Campoy, C., Colomb, V., Decsi, T., Fewtrell, M., Hojsak, I., Mihatsch, W., Molgaard, C., Shamir, R., Turck, D. y van Goudoever, J. (2014). Iron requirements of infants and toddlers. Journal of Pediatric Gastroenterology and Nutrition, 58(1), 119-129. https://doi.org/10.1097/MPG.0000000000000206
Fuqua, B. K., Vulpe, C. D. y Anderson, G. J. (2012). Intestinal iron absorption. Journal of Trace Elements in Medicine and Biology, 26(2-3), 115-119. https://doi.org/10.1016/j.jtemb.2012.03.015
Galicia, L., Grajeda, R. y López de Romaña, D. (2016). Nutrition situation in Latin America and the Caribbean: Current scenario, past trends, and data gaps. Revista Panamericana de Salud Pública, 40(2), 104-113.
Gouda, R., Baishya, H. y Qing, Z. (2017). Application of mathematical models in drug release kinetics of carbidopa and levodopa ER tablets. Journal of Developing Drugs, 6(2), 1000171. https://doi.org/10.4172/2329-6631.1000171
Higuchi, T. (1963). Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. Journal of Pharmaceutical Sciences, 52(12), 1145-1149. https://doi.org/10.1002/jps.2600521210
Hubatsch, I., Ragnarsson, E. y Artursson, P. (2007). Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nature Protocols, 2, 2111-2119. https://doi.org/10.1038/nprot.2007.303
Hunter, A. C., Elsom, J., Wibroe, P. P. y Moghimi, S. M. (2012). Polymeric particulate technologies for oral drug delivery and targeting: A pathophysiological perspective. Maturitas, 73(1), 5-18. https://doi.org/10.1016/j.maturitas.2012.05.014
Igbinosa, I., Berube, C. y Lyell, D. J. (2022). Iron deficiency anemia in pregnancy. Current Opinion in Obstetrics and Gynecology, 34(2), 69-76. https://doi.org/10.1097/GCO.0000000000000772
Kalinowski, D. S. y Richardson, D. R. (2005). The evolution of iron chelators for the treatment of iron overload disease and cancer. Pharmacological Reviews, 57(4), 547-583. https://doi.org/10.1124/pr.57.4.2
Khongkow, M., Rimsueb, N., Jantimaporn, A., Janyaphisan, T., Woraprayote, W., Visessanguan, W. y Ruktanonchai, U. R. (2023). Cationic liposome of hen egg white lysozyme for enhanced its stability, activity and accessibility in gastro-intestinal tract. Food Bioscience, 53, 102470. https://doi.org/10.1016/j.fbio.2023.102470
Kim, J. H., Jeon, T. Y., Choi, T. M., Shim, T. S., Kim, S.-H. y Yang, S.-M. (2014). Droplet microfluidics for producing functional microparticles. Langmuir, 30(6), 1473-1488. https://doi.org/10.1021/la403220p
Korsmeyer, R. W., Gurny, R., Doelker, E., Buri, P. y Peppas, N. A. (1983). Mechanisms of solute release from porous hydrophilic polymers. International Journal of Pharmaceutics, 15(1), 25-35. https://doi.org/10.1016/0378-5173(83)90064-9
Larson, L. M., Cyriac, S., Djimeu, E. W., Mbuya, M. N. y Neufeld, L. M. (2021). Can double fortification of salt with iron and iodine reduce anemia, iron deficiency anemia, iron deficiency, iodine deficiency, and functional outcomes? Evidence of efficacy, effectiveness, and safety. The Journal of Nutrition, 151(1), 15S-28S. https://doi.org/10.1093/jn/nxaa192
Liga, A., Morton, J. A. y Kersaudy-Kerhoas, M. (2016). Safe and cost-effective rapid-prototyping of multilayer PMMA microfluidic devices. Microfluidics and Nanofluidics, 20, 164. https://doi.org/10.1007/s10404-016-1823-1
Losco De Cusatis, L., de Gregorio, M. S., Carbone, S., Crispino, R., Tammaro, D. y Di Natale, C. (2026). Microfluidics for particle production in drug delivery: From physical basics to perspective applications. TrAC Trends in Analytical Chemistry, 204, 119076. https://doi.org/10.1016/j.trac.2026.119076
Lukova, P. y Katsarov, P. (2023). Contemporary aspects of designing marine polysaccharide microparticles as drug carriers for biomedical application. Pharmaceutics, 15(8), 2126. https://doi.org/10.3390/pharmaceutics15082126
Ma, L., Zhao, X., Hou, J., Xiao, Y., Lu, X., Chen, Z, Wei, J. y Hao, N. (2026). Droplet microfluidics for biomedical applications: Emerging trends and future developments. Microsystems & Nanoengineering, 12, 53. https://doi.org/10.1038/s41378-026-01175-7
Maas, L. A., Krishna, M. y Parian, A. M. (2023). Ironing it all out: A comprehensive review of iron deficiency anemia in inflammatory bowel disease patients. Digestive Diseases and Sciences, 68, 357-369. https://doi.org/10.1007/s10620-022-07599-1
Marengo, R. C., Mengatto, L. N., Olivares, M. L. y Berli, C. L. (2021). Microfluidics-based encapsulation of isoniazid in egg white/carrageenan microparticles for sustained release. Food Hydrocolloids for Health, 1, 100041. https://doi.org/10.1016/j.fhfh.2021.100041
Marengo, R. C., Olivares, M. L. y Berli, C. L. (2019). Generation of egg white/carrageenan microparticles by droplet-based microfluidics. Journal of Food Engineering, 259, 21-28. https://doi.org/10.1016/j.jfoodeng.2019.04.019.
Miret, S., Tascioglu, S., van der Burg, M., Frenken, L. y Klaffke, W. (2010). In vitro bioavailability of iron from the heme analogue sodium iron chlorophyllin. Journal of Agricultural and Food Chemistry, 58(2), 1327-1332. https://doi.org/10.1021/jf903177q
Piskin, E., Cianciosi, D., Gulec, S., Tomas, M. y Capanoglu, E. (2022). Iron absorption: Factors, limitations, and improvement methods. ACS Omega, 7(24), 20441-20456. https://doi.org/10.1021/acsomega.2c01833
Skolmowska, D. y Głąbska, D. (2019). Analysis of heme and non-heme iron intake and iron dietary sources in adolescent menstruating females in a national polish sample. Nutrients, 11(5), 1049. https://doi.org/10.3390/nu11051049
Span, K., Verhoef, J. J., Hunt, H., van Nostrum, C. F., Brinks, V., Schellekens, H. y Hennink, W. E. (2016). A novel oral iron-complex formulation: Encapsulation of hemin in polymeric micelles and its in vitro absorption. European Journal of Pharmaceutics and Biopharmaceutics, 108, 226-234. http://doi.org/10.1016/j.ejpb.2016.09.002
Valenzuela, C., López de Romaña, D., Olivares, M., Morales, M. S. y Pizarro, F. (2009). Total iron and heme iron content and their distribution in beef meat and viscera. Biological Trace Element Research, 132, 103-111. https://doi.org/10.1007/s12011-009-8400-3
Vatandoust, A. y Diosady, L. (2022). Iron compounds and their organoleptic properties in salt fortification with iron and iodine: An overview. Current Opinion in Food Science, 43, 232-236. https://doi.org/10.1016/j.cofs.2021.12.007
Villarroel, P., Flores, S., Pizarro, F., López de Romaña, D. y Arredondo, M. (2011). Effect of dietary protein on heme iron uptake by Caco-2 cells. European Journal of Nutrition, 50, 637-643. https://doi.org/10.1007/s00394-011-0173-8
Wu, I. Y., Bala, S., Skalko-Basnet, N. y di Cagno, M. P. (2019). Interpreting non-linear drug diffusion data: Utilizing Korsmeyer-Peppas model to study drug release from liposomes. European Journal of Pharmaceutical Sciences, 138, 105026. https://doi.org/10.1016/j.ejps.2019.105026
Wu, S., Liu, S., Li, Y. y Feng, J. (2024). Recent research advances in delivery systems based on the assembly of egg white proteins: Structure design and applications in the food industry. Food Hydrocolloids, 153, 110021. https://doi.org/10.1016/j.foodhyd.2024.110021
Xu, X., Tang, Q., Gao, Y., Chen, S., Yu, Y., Qian, H., McClements, D. C., Cao, C. y Yuan, B. (2025). Recent developments in the fabrication of food microparticles and nanoparticles using microfluidic systems. Critical Reviews in Food Science and Nutrition, 65(12), 2199-2213. https://doi.org/10.1080/10408398.2024.2329967
Yermak, I. M., Davydova, V. N. y Volod’ko, A. V. (2022). Mucoadhesive marine polysaccharides. Marine Drugs, 20(8), 522. https://doi.org/10.3390/md20080522
Yermak, I. M., Davydova, V. N., Kravchenko, A. O., Chistyulin, D. A., Pimenova, E. A. y Glazunov, V. P. (2020). Mucoadhesive properties of sulphated polysaccharides carrageenans from red seaweed families Gigartinaceae and Tichocarpaceae. International Journal of Biological Macromolecules, 142, 634-642. https://doi.org/10.1016/j.ijbiomac.2019.10.005
Zahra, F., Hashmi, A. R., Ravi, R. N., Sekar, M., Wong, L. S., Jaganathan, R. y Ravindran, R. (2026). Advances in mucoadhesive drug delivery systems: Mechanistic insights, pharmacological performance, and translational pathways. Current Research in Pharmacology and Drug Discovery, 11, 100261. https://doi.org/10.1016/j.crphar.2026.100261
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Derechos de autor 2026 Robinson Cristian Marengo, Marianela Masin, Luciano Mengatto, Claudio Berli, María Laura Olivares
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