ФУКОИДАН КАК КОМПОНЕНТ ПРИ РАЗРАБОТКЕ ТАРГЕТНЫХ СИСТЕМ ДОСТАВКИ ЛЕКАРСТВЕННЫХ ВЕЩЕСТВ

DOI: https://doi.org/10.29296/24999490-2019-05-03

В.Е. Супрунчук, аспирант, ассистент, Е.В. Денисова, кандидат биологических наук, доцент ФГАОУ ВО «Северо-Кавказский федеральный университет», Российская Федерация, 355009, Ставрополь, Пушкина, 1а E-mail: vikasuprunchuk@gmail.com

Растущий интерес к группе высокосульфатированных гетерополисахаридов, определяемых как фукоиданы, обусловлен широким спектром их биологической активности. Расширение направления их приложения связано с поиском возможностей их применения при разработке материалов медицинского назначения, в частности таргетной системы доставки лекарственных веществ. Основными видами нано- и микроструктурных систем, созданных с использованием фукоидана, являются объекты, формируемые за счет сил электростатического притяжения разноименно заряженных полиэлектролитов (послойная адсорбция, полиэлектролитные комплексы), эмульсии, металлполимерные комплексы. Использование фукоидана как покрытия для биомагнетиков также позволяет применять его в тераностике. Полученные носители, содержащие фукоидан, применимы для адресной доставки таких терапевтических агентов, как доксорубицин, куркумин, поли-L-лизин, низкомолекулярные противотуберкулезные препараты и т.д. Способ доставки также варьируется. Разрабатываются носители с применением фукоидана для перорального, ингаляционного, внутривенного способа введения. При этом такие системы обладают низкой токсичностью, биодеградируемы. Продукты деградации не накапливаются в организме, а метаболизируются. Кроме того, возможно получение полых матриц с высокой степенью загрузки. Все это позволят расширить возможности применения данного полисахарида в фармацевтической промышленности и клинической терапии.

Список литературы: 
  1. Kloareg B., Demarty M., Mabeau S. Polyanionic characteristics of purified sulphated homofucans from brown algae. Int J. Biol. Macromol. 1986; 8 (6): 380–6.
  2. Cong Q., Chen H., Liao W., Xiao F., Wang P., Qin Y., Dong Q., Ding K. Structural characterization and effect on anti-angiogenic activity of a fucoidan from Sargassum fusiforme. Carbohydr Polym. 2016; 136: 899–907.
  3. Ale M.T., Maruyama H., Tamauchi H., Mikkelsen J.D., Meyer A.S. Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo. Int J. Biol. Macromol. 2011; 49 (3): 331–6.
  4. Vinnitskiy D.Z., Krylov V.B., Ustyuzhanina N.E., Dmitrenok A.S., Nifantiev N.E. The synthesis of heterosaccharides related to the fucoidan from Chordaria flagelliformis bearing an α- α-L-fucofuranosyl unit. Org Biomol Chem [Internet]. 2016; 14 (2): 598–611. Available from: http://xlink.rsc.org/?DOI=C5OB02040A
  5. Одинец А.Г., Татаринова Л.В. Фукоидан:современные представления о его роли в регуляции углеводного обмена. В мире лекарств. 2016; 3 (49): 40–4. [Odinets A.G., Tatarinova L.V. Fucoidan: modern ideas about its role in the regulation of carbohydrate metabolism. In the world of medicine. 2016; 3 (49): 40–4 (in Russian)]
  6. Мухамеджанов Э.К., Есырев О.В. Фукоидан – натуральный протектор ЖКТ. In: Гастроэнтерология Санкт-Петербурга. 2016; 17–8. [Mukhamedzhanov E.C., Esyrev O.V. Fucoidan is a natural protector of the digestive tract. In: Gastroenterology of St. Petersburg. 2016; 17–8 (in Russian)]
  7. Санина Т.В., Кирьянова С.В., Черемушкина И.В., Корнеева О.С. Исследование бифидогенной активности фукозы и ее полимеров. Вестник ВГУ, серия Химия Биология Фармация. 2011; 1: 141–3. [Sanina T.V., Kiryanova S.V., Cheremushkina I.V., Korneyev O.S. Study of bifidogenic activity of fucose and its polymers. Herald of VSU, Chemistry Biology Pharmacy series. 2011; 1: 141–3 (in Russian)]
  8. Беседнова Н.Н., Макаренкова И.Д., Звягинцева Т.Н., Кузнецова Т.А., Запорожец Т.С. Ингибирующее действие полисахаридов морских гидробионтов на формирование биопленок. Антибиотики и химиотерапия. 2016; 61: 9–10. [Besednova N.N., Makarenkova I.D., Zvyagintseva T.N., Kuznetsova T.A., Zaporozhets T.S. Inhibitory effect of marine hydrobiont polysaccharides on biofilm formation. Antibiotics and chemotherapy. 2016; 61: 9–10 (in Russian)]
  9. Кательникова А.Е., Макаров В.Г., Воробьева В.В., Пожарицкая О.Н., Шиков А.Н., Шабанов П.Д. Перспективы использования лекарственных средств на основе гидробионтов в лечении респираторных вирусных инфекций и их осложнений. Обзоры по клинической фармакологии и лекарственной терапии. 2017; 15 (1): 4–13. [Katelnikova A.E., Makarov V.G., Vorobyov V.V., Pozharitskaya O.N., Shikov A.N., Shabanov P.D. Prospects for the use of drugs based on hydrobionts in the treatment of respiratory viral infections and their complications. Reviews of clinical pharmacology and drug therapy. 2017; 15 (1): 4–13 (in Russian)]
  10. Макаренкова И.Д., Леонова Г.Н., Майстровская О.С., Звягинцева Т.Н., Имбс Т.И., Ермакова С.П., Беседнова Н.Н. Противовирусная активность сульфатированных полисахаридов из бурых водорослей при экспериментальном клещевом энцефалите : связь структуры и функции. Тихоокеанский медицинский журнал. 2012; 1: 44–6. [Makarenkova I.D., Leonov G.N., Maistrovskaya O.S., Zvyagintseva T.N., Imb T.I., Ermakova S.P., Besednova N.N. Antiviral activity of sulfated polysaccharides from brown algae in experimental tick-borne encephalitis: the relationship of structure and function. Pacific Medical J. 2012; 1: 44–6 (in Russian)]
  11. Крыжановский С.П., Богданович Л.Н., Кнышова В.В., Персиянова Е.В., Запорожец Т.С., Звягинцева Т.Н. Влияние полисахаридов бурых водорослей на процессы липопероксидации и антиоксидантной защиты у пациентов с дислипидемией. In: Материалы Научно-практической конференции «Фундаментальная дальневосточная наука – медицине». 2017; 93–7. [Kryzhanovsky S.P., Bogdanovich L.N., Knyshova V.V., Persianova E.V., Zaporozhets T.S., Zvyagintseva T.N. The effect of brown algae polysaccharides on the processes of lipid peroxidation and antioxidant protection in patients with dyslipidemia. In: Materials of the Scientific and Practical Conference «Fundamental Far Eastern Science – Medicine». 2017; 93–7 (in Russian)]
  12. Одинец А.Г., Орлов О.И., Ильин В.К., Ревина А.А., Антропова И.Г., Фенин А.А., Татаринова Л.В., Прокофьев А.С. Радиопротективные и антиоксидантные свойства геля из бурых морских водорослей. Вестник восстановительной медицины. 2015; 89–96. [Odinets A.G., Orlov O.I., Ilyin V.K., Revina A.A., Antropova I.G., Fenin A.A., Tatarinova L.V., Prokofiev A.S. Radioprotective and antioxidant properties of the gel from brown algae. Bulletin of restorative medicine. 2015; 89–96 (in Russian)]
  13. Урванцева А.М., Бакунина И.Ю., Ким Н.Ю., Исаков В.В., Глазунов В.П., Звягинцева Т.Н. Выделение очищенного фукоидана из природного комплекса с полифенолами и его характеристика. Химия растительного сырья. Химия растительного сырья. 2004; (3): 15–24. [Urvantseva A.M., Bakunin U.Y., Kim N.Y., Isakov V.V., Glazunov V.P., Zvyagintsev T.N. Isolation of purified fucoidan from a natural complex with polyphenols and its characteristic. Chemistry of plant raw materials. Chemistry of plant materials. 2004; (3): 15–24 (in Russian)]
  14. Baba B.M., Mustapha W.A.W., Joe L.S. Effects of extraction solvent on fucose content in fucoidan extracted from brown seaweed (Sargassum sp.) from Pulau Langkawi, Kedah, Malaysia. In: AIP Conference Proceedings. AIP Publishing. 2016; 030045-1-030045–5.
  15. Fitton J.H., Stringer D.N., Karpiniec S.S. Therapies from fucoidan: An update. Mar Drugs. 2015; 13 (9): 5920–46.
  16. Holtkamp A.D., Kelly S., Ulber R., Lang S. Fucoidans and fucoidanases-focus on techniques for molecular structure elucidation and modification of marine polysaccharides. Appl Microbiol Biotechnol. 2009; 82 (1): 1–11.
  17. Yuan Y., Macquarrie D. Microwave assisted extraction of sulfated polysaccharides (fucoidan) from Ascophyllum nodosum and its antioxidant activity. Carbohydr Polym [Internet]. 2015 Sep 20 [cited 2018 Aug 8]; 129: 101–7. Available from: https://www.sciencedirect.com/science/article/pii/S0144861715003732
  18. Li B., Lu F., Wei X., Zhao R. Fucoidan: Structure and bioactivity. Molecules. 2008; 13 (8): 1671–95.
  19. Bruhn A., Janicek T., Manns D., Nielsen M.M., Balsby T.J.S., Meyer A.S., Rasmussen M.B., Hou X., Saake B., Göke C., Bjerre A.B. Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata–seasonal variation and impact of environmental factors. J Appl Phycol. 2017; 29 (6): 3121–37.
  20. Khatuntseva E.A., Ustuzhanina N.E., Zatonskii G.V., Shashkov A.S., Usov A.I., Nifant’ev N.E. Synthesis, NMR and Conformational Studies of Fucoidan Fragments 1: Desulfated 2,3- and 3,4-Branched Trisaccharide Fragments and Constituting Disaccharides. J. Carbohydr Chem. 2000.
  21. Cumashi A., Ushakova N.A., Preobrazhenskaya M.E., D’Incecco A., Piccoli A., Totani L., Tinari N., Morozevich G.E., Berman A.E., Bilan M.I., Usov A.I., Ustyuzhanina N.E., Grachev A.A., Sanderson C.J., Kelly M., Rabinovich G.A., Iacobelli S., Nifantiev N.E. A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiology. 2007; 17 (5): 541–52.
  22. Reddy L.C.N., Reddy R.S.P., Rao K.K.S.V., Subha M.C.S., Rao C.K. Development of polymeric blend microspheres from chitosan- hydroxypropylmethyl cellulose for controlled release of an anti-cancer drug. J. Korean Chem Soc. 2013; 57 (14): 439–46.
  23. Berkland C., King M., Cox A., Kim K. (Kevin), Pack D.W. Precise control of PLG microsphere size provides enhanced control of drug release rate. J. Control. Release [Internet]. 2002 Jul 18 [cited 2018 Aug 19]; 82 (1): 137–47. Available from: https://www.sciencedirect.com/science/article/pii/S0168365902001360
  24. Antipov A.A., Sukhorukov G.B. Polyelectrolyte multilayer capsules as vehicles with tunable permeability. Adv Colloid Interface Sci. 2004; 111 (1): 49–61.
  25. Pastorino L., Dellacasa E., Noor M.R., Soulimane T., Bianchini P., D’Autilia F., Antipov A., Diaspro A., Tofail S.A.M., Ruggiero C. Multilayered polyelectrolyte microcapsules: Interaction with the enzyme cytochrome c oxidase. PLoS One. 2014; 9 (11): 5–11.
  26. Venkatesan J., Anil S., Kim S.-K., Shim M. Seaweed Polysaccharide-Based Nanoparticles: Preparation and Applications for Drug Delivery. Polymers (Basel). 2016; 8 (2): 30.
  27. Jamshidi A., Shabanpour B., Pourashouri P., Raeisi M. Using WPC-inulin-fucoidan complexes for encapsulation of fish protein hydrolysate and fish oil in W1/O/W2 emulsion: Characterization and nutritional quality. Food Res Int [Internet]. 2018 Dec 1 [cited 2018 Aug 19]; 114: 240–50. Available from: https://www.sciencedirect.com/science/article/pii/S0963996918306045
  28. Hwang P.A., Lin X.Z., Kuo K.L., Hsu F.Y. Fabrication and cytotoxicity of fucoidan-cisplatin nanoparticles for macrophage and tumor cells. Materials (Basel). 2017; 10 (3): 291-1-291–10.
  29. Silva T.H., Alves A., Popa E.G., Reys L.L., Gomes M.E., Sousa R.A., Silva S.S., Mano J.F., Reis R.L. Marine algae sulfated polysaccharides for tissue engineering and drug delivery approaches. Biomatter. 2012; 2 (4): 278–89.
  30. Tako M. Rheological characteristics of fucoidan isolated from commercially cultured Cladosiphon okamuranus. Bot Mar. 2003; 46 (5): 461–5.
  31. Fan J., Liu Y., Wang S., Liu Y., Li S., Long R., Zhang R., Kankala R.K. Synthesis and characterization of innovative poly(lactide-co-glycolide)-(poly-L-ornithine/ fucoidan) core–shell nanocarriers by layer-by-layer self-assembly. RSC Adv. 2017; 7: 32786–94.
  32. Kim D.Y., Shin W.S. Unique characteristics of self-assembly of bovine serum albumin and fucoidan, an anionic sulfated polysaccharide, under various aqueous environments. Food Hydrocoll. 2015; 44: 471–7.
  33. Kim D.-Y., Shin W.-S. Functional improvements in bovine serum albumin–fucoidan conjugate through the Maillard reaction. Food Chem [Internet]. 2016 Jan 1 [cited 2018 Aug 17]; 190: 974–81. Available from: https://www.sciencedirect.com/science/article/pii/S0308814615009383
  34. Sezer A.D., Akbuǧa J. Fucosphere – New microsphere carriers for peptide and protein delivery: Preparation and in vitro characterization. J Microencapsul. 2006; 23 (5): 513–22.
  35. Sezer A.D., Cevher E., Hatipoǧlu F., Oǧurtan Z., Baş A.L., Akbuǧa J. The use of fucosphere in the treatment of dermal burns in rabbits. Eur J Pharm Biopharm. 2008; 69 (1): 189–98.
  36. Lee E.J., Lim K.-H. Relative charge density model on chitosan–fucoidan electrostatic interaction: Qualitative approach with element analysis. J Biosci Bioeng [Internet]. 2015 Feb 1 [cited 2018 Aug 20]; 119 (2): 237–46. Available from: https://www.sciencedirect.com/science/article/pii/S1389172314002552
  37. Liu Y., Yao W., Wang S., Geng D., Zheng Q., Chen A. Preparation and Characterization of Fucoidan-Chitosan Nanospheres by the Sonification Method. J. Nanosci Nanotechnol. 2014; 14 (5): 3844–9.
  38. Huang Y.C., Li R.Y. Preparation and characterization of antioxidant nanoparticles composed of chitosan and fucoidan for antibiotics delivery. Mar Drugs. 2014; 12 (8): 4379–98.
  39. Huang Y.C., Chen J.K., Lam U.I., Chen S.Y. Preparing, characterizing, and evaluating chitosan/fucoidan nanoparticles as oral delivery carriers. J. Polym Res. 2014; 21 (5): 415: 1–9.
  40. Lu K.Y., Li R., Hsu C.H., Lin C.W., Chou S.C., Tsai M.L., Mi F.L. Development of a new type of multifunctional fucoidan-based nanoparticles for anticancer drug delivery. Carbohydr Polym. 2017; 165: 410–20.
  41. Kumari A., Yadav S.K., Yadav S.C. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surfaces B Biointerfaces [Internet]. 2010 Jan 1 [cited 2018 Aug 20]; 75 (1): 1–18. Available from: https://www.sciencedirect.com/science/article/pii/S0927776509004111
  42. Ravivarapu H., Mahalingam R., Jasti B.R. Design of Controlled Release Drug Delivery Systems. Des Control Release Drug Deliv Syst. 2006; 271–303.
  43. Ravivarapu H.B., Lee H., DeLuca P.P. Enhancing initial release of peptide from poly(d,l-lactide-co-glycolide) (PLGA) microspheres by addition of a porosigen and increasing drug load. Pharm Dev Technol. 2000; 5 (2): 287–96.
  44. Ravivarapu H.B., Burton K., DeLuca P.P. Polymer and microsphere blending to alter the release of a peptide from PLGA microspheres. Eur J Pharm Biopharm [Internet]. 2000 Sep 1 [cited 2018 Aug 20]; 50 (2): 263–70. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0939641100000990
  45. Ferreira S.A. Development of fucoidan/chitosan nanoparticulate systems for protein administration through mucosal routes. 2012.
  46. Sezer A.D., Akbuğa J. The design of biodegradable ofloxacin-based core-shell microspheres: Influence of the formulation parameters on in vitro characterization. Pharm Dev Technol. 2012; 17 (1): 118–24.
  47. Chandur V.K., Badiger A.M., Rao K.R.S.S. Characterizing formulations containing derivatized chitosan with polymer blending. Int J. Res Pharm Chem [Internet]. 2011; 4 (1): 950–67. Available from: www.ijrpc.com
  48. Sezer A.D., Akbuğa J. Comparison on In Vitro Characterization of Fucospheres and Chitosan Microspheres Encapsulated Plasmid DNA (pGM-CSF): Formulation Design and Release Characteristics. AAPS PharmSciTech. 2009; 10 (4): 1193–9.
  49. Wu S.J., Don T.M., Lin C.W., Mi F.L. Delivery of berberine using chitosan/fucoidan-taurine conjugate nanoparticles for treatment of defective intestinal epithelial tight junction barrier. Mar Drugs. 2014; 12 (11): 5677–97.
  50. Yu S.-H., Wu S.-J., Wu J.-Y., Wen D.-Y., Mi F.-L. Preparation of fucoidan-shelled and genipin-crosslinked chitosan beads for antibacterial application. Carbohydr Polym [Internet]. 2015 Aug 1 [cited 2018 Aug 20]; 126: 97–107. Available from: https://www.sciencedirect.com/science/article/pii/S0144861715002131
  51. Da Silva L.C., Garcia T., Mori M., Sandri G., Bonferoni M.C., Finotelli P.V., Cinelli L.P., Caramella C., Cabral L.M. Preparation and characterization of polysaccharide-based nanoparticles with anticoagulant activity. Int J. Nanomedicine. 2012; 7: 2975–86.
  52. Chen M.C., Wong H.S., Lin K.J., Chen H.L., Wey S.P., Sonaje K., Lin Y.H., Chu C.Y., Sung H.W. The characteristics, biodistribution and bioavailability of a chitosan-based nanoparticulate system for the oral delivery of heparin. Biomaterials. 2009; 30 (34): 6629–37.
  53. Pinheiro A.C., Bourbon A.I., Cerqueira M.A., Maricato É., Nunes C., Coimbra M.A., Vicente A.A. Chitosan/fucoidan multilayer nanocapsules as a vehicle for controlled release of bioactive compounds. Carbohydr Polym. 2015; 115: 1–9.
  54. Huang Y.-C., Kuo T.-H. O-carboxymethyl chitosan/fucoidan nanoparticles increase cellular curcumin uptake. Food Hydrocoll [Internet]. 2016 Feb 1 [cited 2018 Aug 22]; 53: 261–9. Available from: https://www.sciencedirect.com/science/article/pii/S0268005X15000673
  55. Cunha L., Rodrigues S., da Costa A.M.R., Faleiro M.L., Buttini F., Grenha A. Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy. Polymers (Basel). 2018; 10 (6): 636-1-636–19.
  56. Park S., Hwang S., Lee J. pH-responsive hydrogels from moldable composite microparticles prepared by coaxial electro-spray drying. Chem Eng J [Internet]. 2011 May 1 [cited 2018 Aug 20]; 169 (1–3): 348–57. Available from: https://www.sciencedirect.com/science/article/pii/S1385894711002725
  57. Sezer A.D., Cevher E. Topical drug delivery using chitosan nano- and microparticles. Expert Opin Drug Deliv. 2012; 9 (9): 1129–46.
  58. Lee K.W., Jeong D., Na K. Doxorubicin loading fucoidan acetate nanoparticles for immune and chemotherapy in cancer treatment. Carbohydr Polym [Internet]. 2013 May 15 [cited 2018 Aug 22]; 94 (2): 850–6. Available from: https://www.sciencedirect.com/science/article/pii/S0144861713001574
  59. Bonnard T., Serfaty J.M., Journé C., Ho Tin Noe B., Arnaud D., Louedec L., Derkaoui S.M., Letourneur D., Chauvierre C., Le Visage C. Leukocyte mimetic polysaccharide microparticles tracked in vivo on activated endothelium and in abdominal aortic aneurysm. Acta Biomater [Internet]. 2014; 10 (8): 3535–45. Available from: http://dx.doi.org/10.1016/j.actbio.2014.04.015
  60. Suzuki M., Bachelet-Violette L., Rouzet F., Beilvert A., Autret G., Maire M., Menager C., Louedec L., Choqueux C., Saboural P., Haddad O., Chauvierre C., Chaubet F., Michel J.B., Serfaty J.M., Letourneur D. Ultrasmall superparamagnetic iron oxide nanoparticles coated with fucoidan for molecular MRI of intraluminal thrombus. Nanomedicine. 2015; 14: 91–8.