توسعه و ارزیابی خصوصیات لیپوزوم بهینه‌یابی شده جهت درون‌پوشانی کورکومین

نشریه پژوهشهای علوم و صنایع غذایی ایران

مقاله 5، دوره 19، شماره 1 - شماره پیاپی 79، فروردین و اردیبهشت 1402، صفحه 57-78   

نوع مقاله: مقاله پژوهشی فارسی

شناسه دیجیتال (DOI): 10.22067/ifstrj.2021.73945.1118

نویسندگان

سیده فاطمه موسوی بایگی¹؛ آرش کوچکی^{* 1}؛ بهروز قرآنی²؛ محبت محبی³

¹دانشگاه فردوسی مشهد

²گروه نانوفناوری مواد غذایی، موسسه پژوهشی علوم و صنایع غذایی (RIFST)، کیلومتر 12 بزرگراه آسیایی مشهد-قوچان، صندوق پستی: 356-157-91895، مشهد، ایران

³گروه علوم و صنایع غذایی، دانشکده کشاورزی، دانشگاه فردوسی مشهد

چکیده

کورکومین به‌عنوان یک ترکیب زیست فعال چربی‌دوست دارای خواص سلامتی‌بخش ویژه‌ای می‌باشد اما پایداری کم و حساسیت بالای آن موجب محدودیت دسترسی زیستی این ماده شده است. هدف از این پژوهش طراحی و توسعه سیستم حامل لیپوزومی جهت ریزپوشانی کورکومین است. درون پوشانی ترکیبات حساس از جمله کورکومین در ساختار لیپوزومی، می تواند روشی موثر بر حفاظت آنها طی شرایط هضم دستگاه گوارشی باشد. هدف از این پژوهش، ارزیابی تاثیر میزان لستین (08/0- 02/0 گرم)، نسبت لستین: کلسترول (4- 5/0)، میزان کورکومین (6- 5/1 میلی‌گرم) و زمان تیمار فراصوت (5- 1 دقیقه) بر تولید لیپوزوم‌های حاوی کورکومین بود. نمونه بهینه با آزمون‌های تعیین اندازه ذرات، توزیع اندازه ذرات، پتانسیل زتا و بازده درون پوشانی به روش تکنیک سطح پاسخ تعیین گردید و سپس ماهیت فیزیکی، ساختار مولکولی و همچنین رفتار رهایش کورکومین درون پوشانی شده در سه شرایط شبیه سازی دهان، معده و روده برای نمونه بهینه مورد ارزیابی قرار گرفت. نتایج نشان داد که همه متغیرهای مستقل بر اندازه ذرات لیپوزوم دارای اثر معنی‌دار (01/0>p) بود و افزایش نسبت لستین: کلسترول موجب یکنواختی هرچه بیشتر اندازه ذرات گردید. لستین تنها جزء اثرگذار بر پتانسیل ذرات تعیین شد و افزایش زمان امواج فراصوت موجب افزایش بازده درون پوشانی کورکومین در لیپوزوم گردید. نقطه بهینه تهیه لیپوزوم با بالاترین بازده درون پوشانی (0/1± 02/69 درصد) وکمترین اندازه ذرات (09/0± 174/214 نانومتر)، توزیع اندازه ذرات (02/0± 105/0) و پتانسیل زتا (31/0± 541/16- میلی‌ولت) در شرایط میزان لستین 08/0 گرم، نسبت لستین: کلسترول 4:1، میزان کورکومین 16/4 میلی‎‌گرم و تیمار فراصوت 5 دقیقه توسط نرم‌افزار دیزاین اکسپرت معرفی شد. کورکومین در ذرات کروی لیپوزوم بهینه به حالت آمورف بود. پایداری این لیپوزوم‌ها طی زمان تحت تاثیر دما بوده به‌طوری که در مقایسه با دمای 4درجه سانتی‌گراد، کورکومین بیشتری از لیپوزوم در دمای 25 درجه سانتی‌گراد رهایش یافته بود. همچنین رفتار رهایش کورکومین در شرایط دستگاه گوارش اساس مکانسیم انتشار بود.

کلیدواژه‌ها

بهینه‌یابی؛ رفتار رهایش؛ کورکومین؛ لیپوزوم

مراجع

1. Adhikary, R., Barnes, C.A., Trampel, R.L., Wallace, S.J., Kee, T.W., & Petrich, J.W. (2011). Photoinduced trans-to-cis isomerization of cyclocurcumin. The Journal of Physical Chemistry B 115(36): 10707-10714. https://doi.org/10.1021/jp200080s.
2. Ahmed, K., Li, Y., McClements, D.J., & Xiao, H. (2012). Nanoemulsion-and emulsion-based delivery systems for curcumin: Encapsulation and release properties. Food Chemistry 132(2): 799-807. https://doi.org/10.1016/j.foodchem.2011.11.039.
3. Anand, P., Kunnumakkara, A.B., Newman, R.A., & Aggarwal, B.B. (2007). Bioavailability of curcumin: problems and promises. Molecular Pharmaceutics 4(6): 807-818. https://doi.org/10.1021/mp700113r.
4. Anderson, M., & Omri, A. (2004). The effect of different lipid components on the in vitro stability and release kinetics of liposome formulations. Drug Delivery11(1): 33-39. https://doi.org/10.1080/10717540490265243.
5. Balanč, B., Trifković, K., Đorđević, V., Marković, S., Pjanović, R., Nedović, V., & Bugarski, B. (2016). Novel resveratrol delivery systems based on alginate-sucrose and alginate-chitosan microbeads containing liposomes. Food Hydrocolloids 61: 832-842. https://doi.org/10.1016/j.foodhyd.2016.07.005.
6. Basnet, P., Hussain, H., Tho, I., & Skalko-Basnet, N. (2012). Liposomal delivery system enhances anti-inflammatory properties of curcumin. Journal of Pharmaceutical Sciences101(2): 598-609. https://doi.org/10.1002/jps.22785.
7. Chavhan, S.S., Petkar, K.C., & Sawant, K. (2011). Nanosuspensions in drug delivery: recent advances, patent scenarios, and commercialization aspects. Critical Reviews™ in Therapeutic Drug Carrier Systems 28(5).
8. Chen, H.W., & Chang, Y.W. (2020). Encapsulation of Clitoria ternatea extract in liposomes by synergistic combination of probe‐type ultrasonication and high‐pressure processing. Journal of Food Safety 40(6): e12859. https://doi.org/10.1111/jfs.12859.
9. Chen, L., Bai, G., Yang, S., Yang, R., Zhao, G., Xu, C., & Leung, W. (2014). Encapsulation of curcumin in recombinant human H-chain ferritin increases its water-solubility and stability. Food Research International 62: 1147-1153. https://doi.org/10.1016/j.foodres.2014.05.054.
10. Chen, S., Li, Q., McClements, D.J., Han, Y., Dai, L., Mao, L., & Gao, Y. (2020). Co-delivery of curcumin and piperine in zein-carrageenan core-shell nanoparticles: Formation, structure, stability and in vitro gastrointestinal digestion. Food Hydrocolloids 99: https://doi.org/10.1016/j.foodhyd.2019.105334.
11. Chen, W., Zou, M., Ma, X., Lv, R., Ding, T., & Liu, D. (2019). Co‐encapsulation of EGCG and quercetin in liposomes for optimum antioxidant activity. Journal of Food Science 84(1): 111-120. https://doi.org/10.1111/1750-3841.14405
12. Cheng, C., Peng, S., Li, Z., Zou, L., Liu, W., & Liu, C. (2017). Improved bioavailability of curcumin in liposomes prepared using a pH-driven, organic solvent-free, easily scalable process. RSC Advances 7(42): 25978-25986. https://doi.org/10.1039/C7RA02861J.
13. Cheng, C., Wu, Z., McClements, D.J., Zou, L., Peng, S., Zhou, W., & Liu, W. (2019). Improvement on stability, loading capacity and sustained release of rhamnolipids modified curcumin liposomes. Colloids and Surfaces B: Biointerfaces 183: https://doi.org/10.1016/j.colsurfb.2019.110460.
14. Chi, J., Ge, J., Yue, X., Liang, J., Sun, Y., Gao, X., & Yue, P. (2019). Preparation of nanoliposomal carriers to improve the stability of anthocyanins. LWT, 109, 101-107. https://doi.org/10.1016/j.lwt.2019.03.070.
15. Darandale, S.S., & Vavia, P.R. (2013). Cyclodextrin-based nanosponges of curcumin: formulation and physicochemical characterization. Journal of Inclusion Phenomena and Macrocyclic Chemistry 75(3-4): 315-322. https://doi.org/10.1007/s10847-012-0186-9.
16. El Khoury, E. D., & Patra, D. (2013). Ionic liquid expedites partition of curcumin into solid gel phase but discourages partition into liquid crystalline phase of 1, 2-dimyristoyl-sn-glycero-3-phosphocholine liposomes. The Journal of Physical Chemistry B, 117(33), 9699-9708. https://doi.org/10.1021/jp4061413
17. El-Samaligy, M. S., Afifi, N. N., & Mahmoud, E. A. (2006). Evaluation of hybrid liposomes-encapsulated silymarin regarding physical stability and in vivo performance. International journal of pharmaceutics, 319(1-2), 121-129. https://doi.org/10.1016/j.ijpharm.2006.04.023
18. Fathi, M., Mozafari, M. R., & Mohebbi, M. (2012). Nanoencapsulation of food ingredients using lipid based delivery systems. Trends in food science & technology, 23(1), 13-27. https://doi.org/10.1016/j.tifs.2011.08.003
19. Hasan, M., Belhaj, N., Benachour, H., Barberi-Heyob, M., Kahn, C. J. F., Jabbari, E., ... & Arab-Tehrany, E. (2014). Liposome encapsulation of curcumin: physico-chemical characterizations and effects on MCF7 cancer cell proliferation. International journal of pharmaceutics, 461(1-2), 519-528. https://doi.org/10.1016/j.ijpharm.2013.12.007
20. Hasan, M., Messaoud, G. B., Michaux, F., Tamayol, A., Kahn, C. J., Belhaj, N., ... & Arab-Tehrany, E. (2016). Chitosan-coated liposomes encapsulating curcumin: Study of lipid–polysaccharide interactions and nanovesicle behavior. RSC advances, 6(51), 45290-45304. https://doi.org/10.1039/C6RA05574E
21. Huh, N. W., Porter, N. A., McIntosh, T. J., & Simon, S. A. (1996). The interaction of polyphenols with bilayers: conditions for increasing bilayer adhesion. Biophysical journal, 71(6), 3261-3277. https://doi.org/10.1016/S0006-3495(96)79519-X
22. Jahanshahi, M., & Mehravar, R. (2009). Protein Nanoparticles as a Novel System for Food Science and Technology. Dynam Biochem Process Biotechnol Mol Biol, 3(2), 1-11.
23. Jain, S., Kumar, D., Swarnakar, N. K., & Thanki, K. (2012). Polyelectrolyte stabilized multilayered liposomes for oral delivery of paclitaxel. Biomaterials, 33(28), 6758-6768. https://doi.org/10.1016/j.biomaterials.2012.05.026
24. Jin, H. H., Lu, Q., & Jiang, J. G. (2016). Curcumin liposomes prepared with milk fat globule membrane phospholipids and soybean lecithin. Journal of dairy science, 99(3), 1780-1790. https://doi.org/10.3168/jds.2015-10391
25. Karewicz, A., Bielska, D., Gzyl-Malcher, B., Kepczynski, M., Lach, R., & Nowakowska, M. (2011). Interaction of curcumin with lipid monolayers and liposomal bilayers. Colloids and Surfaces B: Biointerfaces, 88(1), 231-239. https://doi.org/10.1016/j.colsurfb.2011.06.037
26. Klang, V., Matsko, N.B., Valenta, C., and Hofer, F. 2012. Electron microscopy of nanoemulsions: An essential tool for characterisation and stability assessment. Micron, 43, 43(2-3), 85–103. https://doi.org/10.1016/j.micron.2011.07.014
27. Lähdesmäki, K., Ollila, O. S., Koivuniemi, A., Kovanen, P. T., & Hyvönen, M. T. (2010). Membrane simulations mimicking acidic pH reveal increased thickness and negative curvature in a bilayer consisting of lysophosphatidylcholines and free fatty acids. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1798(5), 938-946. https://doi.org/10.1016/j.bbamem.2010.01.020
28. Laouini, A., Jaafar-Maalej, C., Sfar, S., Charcosset, C., & Fessi, H. (2011). Liposome preparation using a hollow fiber membrane contactor—application to spironolactone encapsulation. International journal of pharmaceutics, 415(1-2), 53-61. https://doi.org/10.1016/j.ijpharm.2011.05.034
29. Li, R., Deng, L., Cai, Z., Zhang, S., Wang, K., Li, L., ... & Zhou, C. (2017). Liposomes coated with thiolated chitosan as drug carriers of curcumin. Materials science and engineering: C, 80, 156-164. https://doi.org/10.1016/j.msec.2017.05.136
30. Li, Z. L., Peng, S. F., Chen, X., Zhu, Y. Q., Zou, L. Q., Liu, W., & Liu, C. M. (2018). Pluronics modified liposomes for curcumin encapsulation: Sustained release, stability and bioaccessibility. Food research international, 108, 246-253. https://doi.org/10.1016/j.foodres.2018.03.048
31. Lin, C. C., Lin, H. Y., Chen, H. C., Yu, M. W., & Lee, M. H. (2009). Stability and characterisation of phospholipid-based curcumin-encapsulated microemulsions. Food Chemistry, 116(4), 923-928. https://doi.org/10.1016/j.foodchem.2009.03.052
32. Liu, Y., Liu, D., Zhu, L., Gan, Q., & Le, X. (2015). Temperature-dependent structure stability and in vitro release of chitosan-coated curcumin liposome. Food research international, 74, 97-105. https://doi.org/10.1016/j.foodres.2015.04.024
33. Lu, Q., Li, D. C., & Jiang, J. G. (2011). Preparation of a tea polyphenol nanoliposome system and its physicochemical properties. Journal of agricultural and food chemistry, 59(24), 13004-13011. https://doi.org/10.1021/jf203194w
34. Lu, Q., Lu, P. M., Piao, J. H., Xu, X. L., Chen, J., Zhu, L., & Jiang, J. G. (2014). Preparation and physicochemical characteristics of an allicin nanoliposome and its release behavior. LWT-Food science and technology, 57(2), 686-695. https://doi.org/10.1016/j.lwt.2014.01.044
35. Madane, R.G., & Mahajan, H.S. (2016). Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration: design, characterization, and in vivo study. Drug Delivery 23(4): 1326-1334. https://doi.org/10.3109/10717544.2014.975382.
36. Maherani, B., Arab-Tehrany, E., Kheirolomoom, A., Geny, D., & Linder, M. (2013). Calcein release behavior from liposomal bilayer; influence of physicochemical/mechanical/structural properties of lipids. Biochimie 95(11): 2018-2033. https://doi.org/10.1016/j.biochi.2013.07.006.
37. Makino, , Yamada, T., Kimura, M., Oka, T., Ohshima, H., & Kondo, T. (1991). Temperature and ionic strength-induced conformational changes in the lipid head group region of liposomes as suggested by zeta potential data. Biophys Chemistry 41: 75-183. https://doi.org/10.1016/0301-4622(91)80017-L.
38. Mohammadi, M., Ghanbarzadeh, B., Hamishehkar, H., Rezayi Mokarram, R., & Mohammadifar, M.A. (2014). Physical properties of vitamin D3-loaded nanoliposomes prepared by thin layer hydration-sonication. Iranian Journal of Nutrition Sciences & Food Technology 8(4): 175-188.
39. Mosca, M., Ceglie, A., & Ambrosone, L. (2011). Effect of membrane composition on lipid oxidation in liposomes. Chemistry and Physics of Lipids 164(2): 158-165. https://doi.org/10.1016/j.chemphyslip.2010.12.006.
40. Mozafari, M.R., Khosravi-Darani, K., Borazan, G.G., Cui, J., Pardakhty, A., & Yurdugul, S. (2008). Encapsulation of food ingredients using nanoliposome technology. International Journal of Food Properties 11(4): 833-844. https://doi.org/10.1080/10942910701648115.
41. Nahr, F.K., Ghanbarzadeh, B., Hamishehkar, H., Kafil, H.S., Hoseini, M., & Moghadam, B.E. (2019). Investigation of physicochemical properties of essential oil loaded nanoliposome for enrichment purposes. LWT 105: 282-289. https://doi.org/10.1016/j.lwt.2019.02.010.
42. Nakajima, M., Wang, Z., Chaudhry, Q., Park, H.J., & Juneja, L.R. (2015). Nano-science-engineering-technology applications to food and nutrition. Journal of Nutritional Science and Vitaminology 61(Supplement): S180-S182.
43. Ng, Z.Y., Wong, J.Y., Panneerselvam, J., Madheswaran, T., Kumar, P., Pillay, V., & Chellappan, D.K. (2018). Assessing the potential of liposomes loaded with curcumin as a therapeutic intervention in asthma. Colloids and Surfaces B: Biointerfaces 172: 51-59. https://doi.org/10.1016/j.colsurfb.2018.08.027.
44. Olbrich, K., Rawicz, W., Needham, D., & Evans, E. (2000). Water permeability and mechanical strength of polyunsaturated lipid bilayers. Biophysical Journal 79(1): 321-327. https://doi.org/10.1016/S0006-3495(00)76294-1.
45. Paini, M., Daly, S.R., Aliakbarian, B., Fathi, A., Tehrany, E.A., Perego, P., & Valtchev, P. (2015). An efficient liposome based method for antioxidants encapsulation. Colloids and Surfaces B: Biointerfaces 136: 1067-1072. https://doi.org/10.1016/j.colsurfb.2015.10.038.
46. Peng, S., Zou, L., Liu, W., Liu, C., & McClements, D.J. (2018). Fabrication and characterization of curcumin-loaded liposomes formed from sunflower lecithin: impact of composition and environmental stress. Journal of Agricultural and Food Chemistry 66(46): 12421-12430. https://doi.org/10.1021/acs.jafc.8b04136.
47. Qazi, H.J., Ye, A., Acevedo-Fani, A., & Singh, H. (2021). In vitro digestion of curcumin-nanoemulsion-enriched dairy protein matrices: Impact of the type of gel structure on the bioaccessibility of curcumin. Food Hydrocolloids 117: 106692. https://doi.org/10.1016/j.foodhyd.2021.106692.
48. Rafiee, Z., Barzegar, M., Sahari, M.A., & Maherani, B. (2017). Nanoliposomal carriers for improvement the bioavailability of high–valued phenolic compounds of pistachio green hull extract. Food Chemistry 220: 115-122. https://doi.org/10.1016/j.foodchem.2016.09.207.
49. Ravichandran, R. (2013). Studies on dissolution behaviour of nanoparticulate curcumin formulation. https://doi.org/10.4236/anp.2013.21010.
50. Reza Mozafari, M., Johnson, C., Hatziantoniou, S., & Demetzos, C. (2008). Nanoliposomes and their applications in food nanotechnology. Journal of Liposome Research 18(4): 309-327. https://doi.org/10.1080/08982100802465941.
51. Schubert, M.A., Harms, M., & Müller-Goymann, C.C. (2006). Structural investigations on lipid nanoparticles containing high amounts of lecithin. European Journal of Pharmaceutical Sciences 27(2-3): 226-236. https://doi.org/10.1016/j.ejps.2005.10.004.
52. Shaikh, J., Ankola, D.D., Beniwal, V., Singh, D., & Kumar, M.R. (2009). Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. European Journal of Pharmaceutical Sciences 37(3-4): 223-230. https://doi.org/10.1016/j.ejps.2009.02.019.
53. Sulkowski, W.W., Pentak, D., Nowak, K., & Sułkowska, A. (2005). The influence of temperature, cholesterol content and pH on liposome stability. Journal of Molecular Structure 744: 737-747. https://doi.org/10.1016/j.molstruc.2004.11.075.
54. Sun, M., Su, X., Ding, B., He, X., Liu, X., Yu, A., & Zhai, G. (2012). Advances in nanotechnology-based delivery systems for curcumin. Nanomedicine 7(7): 1085-1100. https://doi.org/10.2217/nnm.12.80.
55. Tai, K., Rappolt, M., Mao, L., Gao, Y., & Yuan, F. (2020). Stability and release performance of curcumin-loaded liposomes with varying content of hydrogenated phospholipids. Food Chemistry 326: 126973. https://doi.org/10.1016/j.foodchem.2020.126973.
56. Takahashi, M., Uechi, S., Takara, K., Asikin, Y., & Wada, K. (2009). Evaluation of an oral carrier system in rats: bioavailability and antioxidant properties of liposome-encapsulated curcumin. Journal of Agricultural and Food Chemistry 57(19): 9141-9146. https://doi.org/10.1021/jf9013923.
57. Tan, C., Xue, J., Lou, X., Abbas, S., Guan, Y., Feng, B., & Xia, S. (2014). Liposomes as delivery systems for carotenoids: comparative studies of loading ability, storage stability and in vitro release. Food & Function 5(6): 1232-1240. https://doi.org/10.1039/C3FO60498E.
58. Taylor, T.M., Davidson, P.M., Bruce B.D., & Weiss, J. (2005). Ultrasonic spectroscopy and differential scanning calorimetry of liposomal-encapsulated Nisin. Journal of Agricultural and Food Chemistry 53(22): 8722-8728. https://doi.org/10.1021/jf050726k.
59. van Ruth, S.M., & Roozen, J.P. (2000). Influence of mastication and saliva on aroma release in a model mouth system. Food Chemistry 71: 339-345. https://doi.org/10.1016/S0308-8146(00)00186-2.
60. Wijiani, N., Isadiartuti, D., Rijal, M. A. S., & Yusuf, H. (2020). Characterization and dissolution study of micellar curcumin-spray dried powder for oral delivery. International Journal of Nanomedicine 15: 1787.
61. Wink, M. (2010). Functions and biotechnology of plant secondary metabolites. (Second ed.).UK: Blackwell Publishing Ltd, PP. 433.
62. Xia, S., & Xu, S. (2005). Ferrous sulfate liposomes: preparation, stability and application in fluid milk. Food Research International 38: 289-296. https://doi.org/10.1016/j.foodres.2004.04.010.
63. Zhi, K., Wang, R., Wei, J., Shan, Z., Shi, C., & Xia, X. (2021). Self-assembled micelles of dual-modified starch via hydroxypropylation and subsequent debranching with improved solubility and stability of curcumin. Food Hydrocolloids 118: 106809. https://doi.org/10.1016/j.foodhyd.2021.106809.
64. Zou, L., Q., Peng, S.F., Liu, W., Gan, L., Liu, W.L., Liang, R.H., & Chen, X. (2014). Improved in vitro digestion stability of (−)-epigallocatechin gallate through nanoliposome encapsulation. Food Research International 64: 492-499. https://doi.org/10.1016/j.foodres.2014.07.042.