pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»pharmjournal-419Research ArticleФАРМАЦЕВТИЧЕСКАЯ ТЕХНОЛОГИЯ И НАНОТЕХНОЛОГИИPHARMACEUTICAL TECHNOLOGY AND NANOTECHNOLOGYМЕТОДЫ ПОЛУЧЕНИЯ ЛИПОСОМ, ИСПОЛЬЗУЕМЫХ В КАЧЕСТВЕ НОСИТЕЛЕЙ ЛЕКАРСТВЕННЫХ СРЕДСТВ (ОБЗОР)METHODS OF OBTAINING LIPOSOMES, USED AS DRUG DELIVERY SYSTEMS (REVIEW)НовиковаА. А.NovikovaA. A.noemail@neicon.ruКезиманаП.KezimanaP.noemail@neicon.ruСтанишевскийЯ. М.StanishevskiyYa. M.noemail@neicon.ruФГАОУ ВО «Российский университет дружбы народов» (Институт биохимической технологии и нанотехнологии)Peoples' Friendship University of Russia (RUDN University) (Institute of Biochemical Technology and Nanotechnology)20170901201902134138Copyright © Новикова А.А., Кезимана П., Станишевский Я.М., 20192019Новикова А.А., Кезимана П., Станишевский Я.М.Novikova A.A., Kezimana P., Stanishevskiy Y.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmjournal.ru/jour/article/view/419

В статье представлен обзор по основным способам получения липосомальных лекарственных препаратов, таким как конвекционный, звуковой методы, метод высокого давления, метод растворения и удаления детергента и метод испарения с обращением фаз. Показаны проблемы технологии гидрофобных антиоксидантных средств (низкая растворимость и химическая стабильность данных лекарственных веществ) и преимущества липосом для их доставки. Установлено, что наиболее перспективной технологией получения липосом с лекарственными веществами, обладающими антиоксидантными свойствами, является метод гидратации тонкой пленки с дальнейшим озвучиванием.

The article presents an overview of the main methods for producing liposomal medications, such as convectional and acoustic methods, high pressure method, detergent dissolution and removal method and the vapor method with phase inversion. The problems of hydrophobic technology of antioxidant pharmaceuticals (low solubility and chemical stability of such drug) and the advantages of liposomes to deliver them are reported. It is established that the most promising technology of producing liposomes containing drugs with antioxidant effects is a thin film hydration method with further sonication.

липосомыфосфолипидынаправленный транспортметод гидратации тонкой пленкиультразвуковое воздействиеliposomesphospholipidsdirectional transportthin film hydration methodsonicationReferencesT. Stozek. The Effect of Entrapment of Procaine Hydrochloride in Liposomes on Local Anesthetic Action // Pharmazie. 1989. V. 44(7). P. 466-468.T. Stozek. The Effect of Entrapment of Procaine Hydrochloride in Liposomes on Local Anesthetic Action // Pharmazie. 1989. V. 44(7). P. 466-468.B. Haley, E. Frenkel. Nanoparticles for drug delivery in cancer treatment // Urologic Oncology: Seminars and Original Investigations. 2008. V. 26. P. 57-64B. Haley, E. Frenkel. Nanoparticles for drug delivery in cancer treatment // Urologic Oncology: Seminars and Original Investigations. 2008. V. 26. P. 57-64Y. Barenholz. Liposome application: problems and prospects // Curr. Opin. Colloid Interface Sci. 2001. 6. P. 66-77.Y. Barenholz. Liposome application: problems and prospects // Curr. Opin. Colloid Interface Sci. 2001. 6. P. 66-77.M.K. Basu. Liposomal delivery of antileishmanial agents // Journal of Applied Research. 2005. V. 5(1). P. 221-236M.K. Basu. Liposomal delivery of antileishmanial agents // Journal of Applied Research. 2005. V. 5(1). P. 221-236J.K. Vasir, M.K. Reddy, V.D. Labhasetwar. Nanosystems in drug targeting: opportunities and challenges // Current Nanoscience. 2005. V. 1(1). P. 47-64.J.K. Vasir, M.K. Reddy, V.D. Labhasetwar. Nanosystems in drug targeting: opportunities and challenges // Current Nanoscience. 2005. V. 1(1). P. 47-64.Н.Б. Демина. Биофармация - путь к созданию инновационных лекарственных средств // Разработка и регистрация лекарственных средств. 2013. № 5.Н.Б. Демина. Биофармация - путь к созданию инновационных лекарственных средств // Разработка и регистрация лекарственных средств. 2013. № 5.C.G. Thanos, D.F. Emerich. Choroid Plexus Epithelial Cell Transplants for Repair of the Brain // Cellular Transplantation. 2007. P. 399-416.C.G. Thanos, D.F. Emerich. Choroid Plexus Epithelial Cell Transplants for Repair of the Brain // Cellular Transplantation. 2007. P. 399-416.U.K. Nassander, G. Storm, P.A.M. Peeters, D.J.A. Crommelin. Liposomes // Biodegradable polymers as drug delivery systems / Ed. by M. Chasin, R. Langer. - New York: Marcel Dekker, 1990. P. 261-338.U.K. Nassander, G. Storm, P.A.M. Peeters, D.J.A. Crommelin. Liposomes // Biodegradable polymers as drug delivery systems / Ed. by M. Chasin, R. Langer. - New York: Marcel Dekker, 1990. P. 261-338.G. Storm , S.O. Belliot, T. Daemen, D.D. Lasic. Surface modification of nanoparticles to oppose uptake by the mononuclear phagocyte system // Adv. Drug Deliv. Rev. 1995. V. 17. P. 31-48G. Storm , S.O. Belliot, T. Daemen, D.D. Lasic. Surface modification of nanoparticles to oppose uptake by the mononuclear phagocyte system // Adv. Drug Deliv. Rev. 1995. V. 17. P. 31-48A.S. Ulrich. Biophysical aspects of using liposomes as delivery vehicles // Bioscience Reports. 2002. V. 22(2). P. 129-150A.S. Ulrich. Biophysical aspects of using liposomes as delivery vehicles // Bioscience Reports. 2002. V. 22(2). P. 129-150R. Tong, Y. Boucher, S. Kozin. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors // Cancer Res. 2004. V. 64. P. 3731-3736.R. Tong, Y. Boucher, S. Kozin. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors // Cancer Res. 2004. V. 64. P. 3731-3736.D.B. Fenske, P.R. Cullis. Liposomal nanomedicines // Expert Opin. Drug Deliv. 2008. V. 5(1). P. 25-44.D.B. Fenske, P.R. Cullis. Liposomal nanomedicines // Expert Opin. Drug Deliv. 2008. V. 5(1). P. 25-44.Р.А. Мухамадияров, А.В. Веремеев, Н.Е. Марцияш, В.Г. Зинчук. Влияние α-токоферола на динамику процессов липопероксидации в липосомах, полученных методами ультразвуковой сонификации и экструзии, при различных температурах хранения // Фундаментальные исследования 2012. № 6. С. 566-570.Р.А. Мухамадияров, А.В. Веремеев, Н.Е. Марцияш, В.Г. Зинчук. Влияние α-токоферола на динамику процессов липопероксидации в липосомах, полученных методами ультразвуковой сонификации и экструзии, при различных температурах хранения // Фундаментальные исследования 2012. № 6. С. 566-570.A.D. Bangham, M.M. Standish, J.C. Watkins. Diffusion of univalent ions across the lamellae of swollen phospholipids // J. Mol. Biol. 1965. V. 13. P. 238-252.A.D. Bangham, M.M. Standish, J.C. Watkins. Diffusion of univalent ions across the lamellae of swollen phospholipids // J. Mol. Biol. 1965. V. 13. P. 238-252.F. Olson, C.A. Hunt, F.C. Szoka, W.J. Vail, D. Papahadjopoulos. Preparation of liposoms of defined size distribution by extrusion through polycarbonate membranes // Biochim Biophys Acta. 1976. V. 557. P. 9-23.F. Olson, C.A. Hunt, F.C. Szoka, W.J. Vail, D. Papahadjopoulos. Preparation of liposoms of defined size distribution by extrusion through polycarbonate membranes // Biochim Biophys Acta. 1976. V. 557. P. 9-23.S.M. Johnson, A.D. Bangham, M.W. Hill, E.D. Korn. Single bilayer liposomes // Biochim Biophys Acta. 1971. V. 233. P. 820-826.S.M. Johnson, A.D. Bangham, M.W. Hill, E.D. Korn. Single bilayer liposomes // Biochim Biophys Acta. 1971. V. 233. P. 820-826.M.U. Uhumwangho, R.S. Okor. Current trends in the production and biomedical applications of liposomes: a review // JMBR: A Peer-review Journal of Biomedical Sciences.2005. V. 4. № 1. Р. 9-21.M.U. Uhumwangho, R.S. Okor. Current trends in the production and biomedical applications of liposomes: a review // JMBR: A Peer-review Journal of Biomedical Sciences.2005. V. 4. № 1. Р. 9-21.R. Nayar, M.J. Hope, P.R. Cullis. Generation of large unilamellar vesicles from long-chain saturated phosphatidylcholine by extrusion techniques // Biochim Biophys Acta. 1989. V. 986. P. 200-206.R. Nayar, M.J. Hope, P.R. Cullis. Generation of large unilamellar vesicles from long-chain saturated phosphatidylcholine by extrusion techniques // Biochim Biophys Acta. 1989. V. 986. P. 200-206.M.J. Hope, M.B. Bally, G. Webb, P.R. Cullis. Production of large unilamellar vesicles by a rapid extrusion procedure. Characterisation of size distribution, trapped volume and ability to maintain a membrane potential // Biochim Biophys Acta. 1985. V. 812. P. 55-65.M.J. Hope, M.B. Bally, G. Webb, P.R. Cullis. Production of large unilamellar vesicles by a rapid extrusion procedure. Characterisation of size distribution, trapped volume and ability to maintain a membrane potential // Biochim Biophys Acta. 1985. V. 812. P. 55-65.S. Amselem, A. Gabizon, Y. Barenholz. A large-scale method for the preparation of sterile and non pyrogenic liposomal formulations of def ined size distributions for clinical use // Liposome Technology. 2nd Edition / Ed. by G. Gregoriadis. - Boca Raton: CRC Press, 1993. P. 501-525.S. Amselem, A. Gabizon, Y. Barenholz. A large-scale method for the preparation of sterile and non pyrogenic liposomal formulations of def ined size distributions for clinical use // Liposome Technology. 2nd Edition / Ed. by G. Gregoriadis. - Boca Raton: CRC Press, 1993. P. 501-525.T. Schneider, A. Sacfse, G. Robling, M. Brandl. Generation of contrast-carrying liposomes of defined size with a new continuous high pressure extrusion method // Int J Pharm. 1995. V. 119. P. 1-12.T. Schneider, A. Sacfse, G. Robling, M. Brandl. Generation of contrast-carrying liposomes of defined size with a new continuous high pressure extrusion method // Int J Pharm. 1995. V. 119. P. 1-12.J. Brunner, P. Skrabai, H. Hauser. Single bilayer vesicles prepared without sonication. Physicochemical properties // BiochimBiophys Acta. 1976. V. 455. P. 322-331.J. Brunner, P. Skrabai, H. Hauser. Single bilayer vesicles prepared without sonication. Physicochemical properties // BiochimBiophys Acta. 1976. V. 455. P. 322-331.N. Weiner, F. Martin, M. Riox. Liposomes as drug delivery system // Drug Dev Ind Pharm. 1989. V. 15. № 10. Р. 1523-1554.N. Weiner, F. Martin, M. Riox. Liposomes as drug delivery system // Drug Dev Ind Pharm. 1989. V. 15. № 10. Р. 1523-1554.F. Frezard. Liposomes: from biophysics to the design of peptide vaccines // Braz J Biol Res. 1999. V. 32. № 2. Р. 181-189.F. Frezard. Liposomes: from biophysics to the design of peptide vaccines // Braz J Biol Res. 1999. V. 32. № 2. Р. 181-189.F. Szoka, D. Papahadjopoulos. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse phase // Proceeding to the National Academy of Sciences. 1978. V. 75. P. 4194-4198.F. Szoka, D. Papahadjopoulos. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse phase // Proceeding to the National Academy of Sciences. 1978. V. 75. P. 4194-4198.B. Tiwari Sandip, N. Udupa, B.S.S. Rao, P. Uma Devi. Thermosensitive liposomes and localised hyperthermia - an effective bimodality approach for tumour management // Indian Journal of Pharmacology. 2000. V. 32. Р. 214-220.B. Tiwari Sandip, N. Udupa, B.S.S. Rao, P. Uma Devi. Thermosensitive liposomes and localised hyperthermia - an effective bimodality approach for tumour management // Indian Journal of Pharmacology. 2000. V. 32. Р. 214-220.S. Bochicchio, A.A. Barba, G. Grassi, G. Lamberti. Vitamin delivery: Carriers based on nanoliposomes produced via ultrasonic irradiation // LWT - Food Science and Technology. 2016. V. 69. P. 9-16.S. Bochicchio, A.A. Barba, G. Grassi, G. Lamberti. Vitamin delivery: Carriers based on nanoliposomes produced via ultrasonic irradiation // LWT - Food Science and Technology. 2016. V. 69. P. 9-16.N. Liu, H.J. Park. Factors effect on the loading efficiency of Vitamin C loaded chitosan-coated nanoliposomes // Colloids and Surfaces B: Biointerfaces. 2010. V. 76. P. 16-19.N. Liu, H.J. Park. Factors effect on the loading efficiency of Vitamin C loaded chitosan-coated nanoliposomes // Colloids and Surfaces B: Biointerfaces. 2010. V. 76. P. 16-19.Y. Feng, C. Sun, Y. Yangyang, et al. Enhanced oral bioavailability and in vivo antioxidant activity of chlorogenic acid via liposomal formulation // International Journal of Pharmaceutics. 2015.Y. Feng, C. Sun, Y. Yangyang, et al. Enhanced oral bioavailability and in vivo antioxidant activity of chlorogenic acid via liposomal formulation // International Journal of Pharmaceutics. 2015.M. Heinonen, D. Rein, T.M. Satue´- Gracia, J. S.-W. Huang, B. German, E.N. Frankel. Effect of Protein on the Antioxidant Activity of Phenolic Compounds in a Lecithin-Liposome Oxidation System // J. Agric. Food Chem. 1998. V. 46. P. 917-922.M. Heinonen, D. Rein, T.M. Satue´- Gracia, J. S.-W. Huang, B. German, E.N. Frankel. Effect of Protein on the Antioxidant Activity of Phenolic Compounds in a Lecithin-Liposome Oxidation System // J. Agric. Food Chem. 1998. V. 46. P. 917-922.

The authors declare that there are no conflicts of interest present.