safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)safetyrisk-25Research ArticleОБЗОРЫ И ОРИГИНАЛЬНЫЕ СТАТЬИREVIEWS AND ORIGINAL ARTICLESРекомендации по оценке безопасности лекарственных средств, содержащих наночастицыRecommendations for evaluating the safety of medicinal products containing nanoparticlesАляутдинР. Н.AlyautdinR. N.Alyautdin@expmed.ruРомановБ. К.RomanovB. K.noemail@neicon.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияFederal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products», Ministry of Health of the Russian FederationRussian Federation201520022018041022Copyright © Аляутдин Р.Н., Романов Б.К., 20182018Аляутдин Р.Н., Романов Б.К.Alyautdin R.N., Romanov B.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/25

Представлены методические рекомендации по доклинической оценке безопасности лекарственных средств, содержащих наночастицы. В рекомендациях представлены условия проведения исследований острой и хронической токсичности нанопре-паратов,методы их количественной и качественной оценки.

Recommendations for preclinical safety assessment of medicinal products containing nanoparticles are presented. The recommendations provide conditions for research acute and chronic toxicity of nanotherapeutics, methods for their quantitative and qualitative assessments.

нанотехнологиитоксичностьлекарственное средствоnanotechnologytoxicitydrugReferencesBleeker EA, de Jong WH, Geertsma RE, et al. Considerations on the EU definition of a nanomaterial: science to support policy making. Regul Toxicol Pharmacol. 2013;65(1):119-125.Bleeker EA, de Jong WH, Geertsma RE, et al. Considerations on the EU definition of a n anomaterial: science to support policy making. Regul Toxicol Pharmacol. 2013;65(1):119–125.Chang HI, Yeh M-K. Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy. Int J Nanomedicine. 2012;7:49-60.Chang HI, Yeh M-K. Clinical development of li posome-based drugs: formulation, characterization, and therapeutic efficacy. Int J Nanomedicine. 2012;7:49–60.Kessler R. Engineered nanoparticles in consumer products: understanding a new ingredient. Environ Health Perspect. 2011;119(3):a120-a125.Kessler R. Engineered n anoparticles in consumer products: understanding a new ingredient. Environ Health Perspect. 2011;119(3):a120–a125.Vega-Villa KR, Takemoto JK, Yбсez JA, Remsberg CM, Forrest ML, Davies NM. Clinical toxicities of nanocarrier systems. Adv Drug Deliv Rev. 2008;60(8):929-938.Vega-Villa KR, Takemoto JK, Yáñ ez JA, Remsberg CM, Forrest ML, Davies NM. Clinical toxicities of n anocarrier systems. Adv Drug Deliv Rev. 2008;60(8):929−938.des Rieux A, Fievez V, Garinot M, Schneider YJ, Präat V. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release. 2006;116(1):1-27.des Rieux A, Fievez V, Garinot M, Schneider YJ, Préat V. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release. 2006;116(1):1–27.Choi HS, Frangioni JV. Nanoparticles for biomedical imaging: fundamentals of clinical translation. Mol Imaging. 2010;9(6): 291-310.Choi HS, Frangioni JV. Nanoparticles for biomedical imaging: fundamentals of clinical translation. Mol Imaging. 2010;9(6): 291–310.Wick P, Manser P, Limbach LK, et al. The degree and kind of agglomeration affect carbon nano-tube cytotoxicity. Toxicol Lett. 2007;168(2):121-131.Wick P, Manser P, Limbach LK, et al. The degree and kind of agglomeration affect carbon n anotube cytotoxicity. Toxicol Lett. 2007;168(2):121–131.SZiemba B, Matuszko G, Bryszewska M, Klajnert B. Influence of dendrimers on red blood cells. Cell Mol Biol Lett. 2012;17(1):21-35.SZiemba B, Matuszko G, Bryszewska M, Klajnert B. Influence of dendrimers on red blood cells. Cell Mol Biol Lett. 2012;17(1):21–35.Stern ST, McNeil SE. Nanotechnology safety concerns revisited. Toxicol Sci. 2008;101(1):4-21.Stern ST, McNeil SE. Nanotechnology safety concerns revisited. Toxicol Sci. 2008;101(1):4–21.Devalapally H, Chakilam A, Amiji MM. Role of nanotechnology in pharmaceutical product development. J Pharm Sci. 2007;96(10): 2547-2565.Devalapally H, Chakilam A, Amiji MM. Role of n anotechnology in pharmaceutical product development. J Pharm Sci. 2007;96(10): 2547–2565.Naahidi S, Jafari M, Edalat F, Raymond K, Khademhosseini A, Chen P. Biocompatibility of engineered nanoparticles for drug delivery. J Control Release. 2013;166(2):182-194.Naahidi S, Jafari M, Edalat F, Raymond K, Khademhosseini A, Chen P. Biocompatibility of engineered n anoparticles for drug delivery. J Control Release. 2013;166(2):182–194.Petros RA, DeSimone JM. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov. 2010;9(8):615-62.Petros RA, DeSimone JM. Strategies in the design of n anoparticles for therapeutic applications. Nat Rev Drug Discov. 2010;9(8):615–62.Mora-Huertas CE, Fessi H, Elaissari A. Polymer-based nanocapsules for drug delivery. Int J Pharm. 2010;385(1-2):113-14.Mora-Huertas CE, Fessi H, Elaissari A. Polymer-based n anocapsules for drug delivery. Int J Pharm. 2010;385(1–2):113–14.Oberduester G, Maynard A, Donaldson K, et al. Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol. 2005;2.Oberdörster G, Mayn ard A, Don aldson K, et al. Princi ples for characterizing the potential human health effects from exposure to n anomaterials: elements of a screening strategy. Part Fibre Toxicol. 2005;2.NanoMarkets. Доступно на nanomarkets.net/images/uploads/ NMThinFilmPrintedBatteries_08. pdf Файл PDF.NanoMarkets. Доступно на nanomarkets.net/images/uploads/ NMThinFilmPrintedBatteries_08.pdf Файл PDF.Kermanizadeh A, Gaiser BK, Johnston H, D et al. Toxicological effect of engineered nanomaterials on the liver. Brit. J. Pharmacol. 2014, 171: 3980-3987.Kermanizadeh A, Gaiser BK, Johnston H, D et al. Toxicological effect of engineered n anomaterials on the liver. Brit. J. Pharmacol. 2014, 171: 3980-3987.Kettiger H, Schipanski A, Wick P.Engineered nanomaterial uptake and tissue distribution: from cell to organism. International Journal of Nanomedicine. 2013, 8: 3255-3269.Kettiger H, Schi panski A, Wick P .Engineered n anomaterial uptake and tissue distribution: from cell to organism. Intern ation al Journ al of Nanomedicine. 2013, 8: 3255–3269.Руководство по проведению доклинических исследований лекарственных средств. Особенности изучения общетоксического действия лекарственных средств и средств медицинского назначения, содержащих наночастицы.2012. Издание ФГБУ ЦНЦЭМСПЦ.Руководство по проведению доклинических исследований лекарственных средств. Особенности изучения общетоксического действия лекарственных средств и средств медицинского назначения, содержащих наночастицы.2012. Издание ФГБУ «НЦЭМСП».Fleischer CC, Payne CK. Nanoparticle surface charge mediates the cellular receptors used by protein-nanoparticle complexes. J Phys Chem B. 2012;116(30):8901-8907.Fleischer CC, Payne CK. Nanoparticle surface charge mediates the cellular receptors used by protein-n anoparticle complexes. J Phys Chem B. 2012;116(30):8901– 8907.Asha Rani PV, Low Kah Mun G, Hande MP, Valiyaveettil S. Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano. 2009;3(2):279-290.Asha Rani PV, Low Kah Mun G, Hande MP, Valiyaveettil S. Cytotoxicity and genotoxicity of silver n anoparticles in human cells. ACS Nano. 2009;3(2):279–290.Shim J, Seok Kang H, Park WS, et al. Transdermal delivery of mixnoxidil with block copolymer nanoparticles. J Control Release. 2004;97(3):477-484.Shim J, Seok Kang H, Park WS, et al. Transdermal delivery of mixnoxidil with block copolymer n anoparticles. J Control Release. 2004;97(3):477–484.Aggarwal N, Goindi S. Preparation and in vivo evaluation of solid lipid nanoparticles of griseofulvin for dermal use. J Biomed Nanotechnol. 2013;9(4):564-576.Aggarwal N, Goindi S. Preparation and in vivo evaluation of solid li pid n anoparticles of griseofulvin for dermal use. J Biomed Nanotechnol. 2013;9(4):564–576.Dobrovolskaia MA, McNeil SE. Immunological properties of engineered nanomaterials. Nat Nanotechnol. 2007;2(8):469-478.Dobrovolskaia MA, McNeil SE. Immunological properties of engineered n anomaterials. Nat Nanotechnol. 2007;2(8):469–478.Gasser M, Rothen-Rutishauser B, Krug HF, et al. The adsorption of biomolecules to multi-walled carbon nanotubes is influenced by both pulmonary surfactant lipids and surface chemistry. J Nanobiotechnology. 2010;8:31.Gasser M, Rothen-Rutishauser B, Krug HF, et al. The adsorption of biomolecules to multi-walled carbon n anotubes is influenced by both pulmon ary surfactant li pids and surface chemistry. J Nanobiotechnology. 2010;8:31.Gessner A, Waicz R, Lieske A et al. Nanoparticles with decreasing surface hydrophobicities: influence on plasma protein adsorption. Int J Pharm. 2000;196(2):245-249.Gessner A, Waicz R, Lieske A et al. Nanoparticles with decreasing surface hydrophobicities: influence on plasma protein adsorption. Int J Pharm. 2000;196(2):245–249.Downs TR, Crosby ME, Hu T, et al.(2012). Silica nanoparticles administrated at the maximum tolerated dose induce genotoxic effects through an inflammatory reaction while gold nanoparticles do not. Mutat Res 745: 38-50.Downs TR, Crosby ME, Hu T, et al.(2012). Silica n anoparticles administrated at the maximum tolerated dose induce genotoxic effects through an inflammatory reaction while gold n anoparticles do not. Mutat Res 745: 38–50.Аляутдин РН, Романов БК, Меркулов ВА. Особенности распределения фуллереновых наночастиц в организме при проведении доклинических исследований. Безопасность и риск фармакотерапии. 2015. №3. 24-31.Alyautdin RN, Romanov BK, Merculov VA. The distribution of fullerene n anoparticles in the body in preclinical studies. Safety and Risk of Pharmacotherapy.2015;(3): 24-31.Dragoni S, Franco G, Regoli M, Bracciali M et al. (2012). Gold nanoparticles uptake and cytotoxicity assessed on rat liver precision cut slices. Toxicol Sci 128: 186-197.Dragoni S, Franco G, Regoli M, Bracciali M et al. (2012). Gold n anoparticles uptake and cytotoxicity assessed on rat liver precision cut slices. Toxicol Sci 128: 186–197.Sadauskas E, Jacobsen NR, Danscher G, Stoltenberg M et al. (2009). Biodistribution of gold nanoparticles inmouse lung following intratracheal instillation. Chem Cent J 3: 16. doi: 10.1186/1752-153X-3-16.Sadauskas E, Jacobsen NR, Danscher G, Stoltenberg M et al. (2009). Biodistribution of gold n anoparticles inmouse lung following intratracheal instillation. Chem Cent J 3: 16. doi: 10.1186/1752-153X-3-16.Fadeel B (2012). Clear and present danger? Engineered nanoparticles and the immune response. Swiss Med Wkly 142: w13609. doi: 10.4414/smw.2012.13609.Fadeel B (2012). Clear and present danger? Engineered n anoparticles and the immune response. Swiss Med Wkly 142: w13609. doi: 10.4414/smw.2012.13609.Kim S, Choi JE, Choi J et al. (2009).0xidative stress-dependant toxicity of silver nanoparticles in human hepatoma cells. Toxicol in Vitro 23: 1076-1084.Kim S, Choi JE, Choi J et al. (2009).Oxidative stress-dependant toxicity of silver n anoparticles in human hepatoma cells. Toxicol in Vitro 23: 1076–1084.

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