pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»10.33380/2305-2066-2025-14-3-2075pharmjournal-2142Research ArticleМЕТОДЫ АНАЛИЗА ЛЕКАРСТВЕННЫХ СРЕДСТВANALYTICAL METHODSПодходы к контролю качества носителей лекарственных средств (обзор)Approaches to quality control of drug carriers (review)https://orcid.org/0000-0001-5144-3061ЕфремоваУ. А.EfremovaU. A.

197022, г. Санкт-Петербург, ул. Профессора Попова, д. 14, литера А

14A, Prof. Popova str., Saint-Petersburg, 197022

ulyana.efremova@spcpu.ruhttps://orcid.org/0009-0008-2169-7800ЧугуноваП. А.ChugunovaP. A.

197022, г. Санкт-Петербург, ул. Профессора Попова, д. 14, литера А

14A, Prof. Popova str., Saint-Petersburg, 197022

https://orcid.org/0009-0005-5126-0034ПоникаровскаяЕ. С.PonikarovskayaE. S.

197022, г. Санкт-Петербург, ул. Профессора Попова, д. 14, литера А

14A, Prof. Popova str., Saint-Petersburg, 197022

https://orcid.org/0000-0002-2942-1015ТернинкоИ. И.TerninkoI. I.

197022, г. Санкт-Петербург, ул. Профессора Попова, д. 14, литера А

14A, Prof. Popova str., Saint-Petersburg, 197022

Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный химико-фармацевтический университет» Министерства здравоохранения Российской Федерации (ФГБОУ ВО СПХФУ Минздрава России)Saint-Petersburg State Chemical and Pharmaceutical University202502092025143108122Copyright © Ефремова У.А., Чугунова П.А., Поникаровская Е.С., Тернинко И.И., 20252025Ефремова У.А., Чугунова П.А., Поникаровская Е.С., Тернинко И.И.Efremova U.A., Chugunova P.A., Ponikarovskaya E.S., Terninko I.I.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/2142Введение

Введение. Развитие нанотехнологий привело к созданию сложных систем доставки лекарственных средств: липосом, дендримеров, неорганических наночастиц, клеточных систем и полимерных наночастиц. Все эти системы требуют комплексного подхода к контролю качества. В данном обзоре рассматриваются ключевые атрибуты контроля качества, среди которых физико-химические и химические методы анализа, а также актуальные регуляторные требования.

Текст

Текст. Системы доставки лекарственных средств представляют собой перспективные технологии, направленные на повышение безопасности и эффективности фармакотерапии. Многообразие компонентов и сложность структуры создают ряд трудностей при разработке подходов к контролю качества новых носителей. Существующие физические и физико-химические методы анализа активно используются для определения морфологических характеристик носителей, физических характеристик их мембраны, подтверждения структуры субстратов и конечной частицы. Однако отсутствие ряда стандартизованных подходов, в частности для определения дзета-потенциала мембраны частиц, остается серьезным вызовом для ряда исследователей и регуляторных органов.

Заключение

Заключение. В данном обзоре представлена системная характеристика подходов к контролю качества систем доставки и их компонентов, которые существуют в настоящее время. Многообразие методов анализа носителей позволяет наиболее полно оценить качество носителей, однако в дальнейшем необходима гармонизация существующих международных норм с российскими стандартами, что минимизирует риски, связанные с использованием носителей в направленной доставке лекарственных средств.

Introduction

Introduction. The development of nanotechnology has led to the creation of complex drug delivery systems: liposomes, dendrimers, inorganic nanoparticles, cellular systems, and polymer nanoparticles. All these systems require an integrated approach to quality control. This review examines the key attributes of quality control, including physico-chemical and chemical analysis methods, as well as current regulatory requirements.

Text

Text. Drug delivery systems represent promising technologies aimed at improving the safety and effectiveness of pharmacotherapy. The variety of components and complexity of the structure create a number of difficulties in developing approaches to quality control of new media. Existing physical and physico-chemical analysis methods are actively used to determine the morphological characteristics of carriers, the physical characteristics of their membrane, and to confirm the structure of substrates and the final particle. However, the lack of a number of standardized approaches, in particular, for determining the zeta potential of a particle membrane, remains a serious challenge for a number of researchers and regulatory authorities.

Conclusion

Conclusion. This review provides a systematic description of the approaches to quality control of delivery systems and their components that currently exist. The variety of media analysis methods makes it possible to fully assess the quality of media, but in the future it is necessary to harmonize existing international standards with Russian standards, which minimizes the risks associated with the use of media in the targeted delivery of medicines.

носители лекарственных средствлипосомымицеллыстандартизацияконтроль качестваdrug delivery systemsnanocarriersstructure of nanocarriersstandardizationquality controlReferencesWen H., Jung H., Li X. Drug delivery approaches in addressing clinical pharmacology-related issues: opportunities and challenges. The AAPS Journal. 2015;17:1327–1340. DOI: 10.1208/s12248-015-9814-9.Wen H., Jung H., Li X. Drug delivery approaches in addressing clinical pharmacology-related issues: opportunities and challenges. The AAPS Journal. 2015;17:1327–1340. DOI: 10.1208/s12248-015-9814-9.Franzè S., Musazzi U. M., Minghetti P., Cilurzo F. Drug-inmicelles-in-liposomes (DiMiL) systems as a novel approach to prevent drug leakage from deformable liposomes. European Journal of Pharmaceutical Sciences. 2019;130:27–35. DOI: 10.1016/j.ejps.2019.01.013.Franzè S., Musazzi U. M., Minghetti P., Cilurzo F. Drug-inmicelles-in-liposomes (DiMiL) systems as a novel approach to prevent drug leakage from deformable liposomes. European Journal of Pharmaceutical Sciences. 2019;130:27–35. DOI: 10.1016/j.ejps.2019.01.013.Li C., Wang Y., Du Y., Qian M., Jiang H., Wang J., Murthy N., Huang R. Side effects-avoided theranostics achieved by biodegradable magnetic silica-sealed mesoporous polymer-drug with ultralow leakage. Biomaterials. 2018;186:1–7. DOI: 10.1016/j.biomaterials.2018.09.039.Li C., Wang Y., Du Y., Qian M., Jiang H., Wang J., Murthy N., Huang R. Side effects-avoided theranostics achieved by biodegradable magnetic silica-sealed mesoporous polymer-drug with ultralow leakage. Biomaterials. 2018;186:1–7. DOI: 10.1016/j.biomaterials.2018.09.039.Niu M., Lu Y., Hovgaard L., Guan P., Tan Y., Lian R., Qi J., Wu W. Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: The effect of cholate type, particle size and administered dose. European Journal of Pharmaceutics and Biopharmaceutics. 2012;81(2):265–272. DOI: 10.1016/j.ejpb.2012.02.009.Niu M., Lu Y., Hovgaard L., Guan P., Tan Y., Lian R., Qi J., Wu W. Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: The effect of cholate type, particle size and administered dose. European Journal of Pharmaceutics and Biopharmaceutics. 2012;81(2):265–272. DOI: 10.1016/j.ejpb.2012.02.009.Li C., Zhang Y., Wan Y., Wang J., Lin J., Li Z., Huang P. STING-activating drug delivery systems: Design strategies and biomedical applications. Chinese Chemical Letters. 2021;32(5):1615–1625. DOI: 10.1016/j.cclet.2021.01.001.Li C., Zhang Y., Wan Y., Wang J., Lin J., Li Z., Huang P. STING-activating drug delivery systems: Design strategies and biomedical applications. Chinese Chemical Letters. 2021;32(5):1615–1625. DOI: 10.1016/j.cclet.2021.01.001.Atanase L. I. Micellar drug delivery systems based on natural biopolymers. Polymers. 2021;13(3):477. DOI: 10.3390/polym13030477.Atanase L. I. Micellar drug delivery systems based on natural biopolymers. Polymers. 2021;13(3):477. DOI: 10.3390/polym13030477.Jafernik K., Ładniak A., Blicharska E., Czarnek K., Ekiert H., Wiącek A. E., Szopa A. Chitosan-based nanoparticles as effective drug delivery systems—a review. Molecules. 2023;28(4):1963. DOI: 10.3390/molecules28041963.Jafernik K., Ładniak A., Blicharska E., Czarnek K., Ekiert H., Wiącek A. E., Szopa A. Chitosan-based nanoparticles as effective drug delivery systems—a review. Molecules. 2023;28(4):1963. DOI: 10.3390/molecules28041963.Guimarães D., Cavaco-Paulo A., Nogueira E. Design of liposomes as drug delivery system for therapeutic applications. International Journal of Pharmaceutics. 2021;601:120571. DOI: 10.1016/j.ijpharm.2021.120571.Guimarães D., Cavaco-Paulo A., Nogueira E. Design of liposomes as drug delivery system for therapeutic applications. International Journal of Pharmaceutics. 2021;601:120571. DOI: 10.1016/j.ijpharm.2021.120571.Song Z., Lin Y., Zhang X., Feng C., Lu Y., Gao Y., Dong C. Cyclic RGD peptide-modified liposomal drug delivery system for targeted oral apatinib administration: enhanced cellular uptake and improved therapeutic effects. International Journal of Nanomedicine. 2017;12:1941–1958. DOI: 10.2147/IJN.S125573.Song Z., Lin Y., Zhang X., Feng C., Lu Y., Gao Y., Dong C. Cyclic RGD peptide-modified liposomal drug delivery system for targeted oral apatinib administration: enhanced cellular uptake and improved therapeutic effects. International Journal of Nanomedicine. 2017;12:1941–1958. DOI: 10.2147/IJN.S125573.Nehal N., Rohilla A., Sartaj A., Baboota S., Ali J. Folic acid modified precision nanocarriers: charting new frontiers in breast cancer management beyond conventional therapies. Journal of Drug Targeting. 2024;32(8):855–873. DOI: 10.1080/1061186X.2024.2356735.Nehal N., Rohilla A., Sartaj A., Baboota S., Ali J. Folic acid modified precision nanocarriers: charting new frontiers in breast cancer management beyond conventional therapies. Journal of Drug Targeting. 2024;32(8):855–873. DOI: 10.1080/1061186X.2024.2356735.Gagliardi A., Giuliano E., Venkateswararao E., Fresta M., Bulotta S., Awasthi V., Cosco D. Biodegradable polymeric nanoparticles for drug delivery to solid tumors. Frontiers in Pharmacology. 2021;12:601626. DOI: 10.3389/fphar.2021.601626.Gagliardi A., Giuliano E., Venkateswararao E., Fresta M., Bulotta S., Awasthi V., Cosco D. Biodegradable polymeric nanoparticles for drug delivery to solid tumors. Frontiers in Pharmacology. 2021;12:601626. DOI: 10.3389/fphar.2021.601626.Blanco E., Shen H., Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology. 2015;33(9):941–951. DOI: 10.1038/nbt.3330.Blanco E., Shen H., Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology. 2015;33(9):941–951. DOI: 10.1038/nbt.3330.Wang N., Wang T., Li T., Deng Y. Modulation of the physicochemical state of interior agents to prepare controlled release liposomes. Colloids and Surfaces B: Biointerfaces. 2009;69(2):232–238. DOI: 10.1016/j.colsurfb.2008.11.033.Wang N., Wang T., Li T., Deng Y. Modulation of the physicochemical state of interior agents to prepare controlled release liposomes. Colloids and Surfaces B: Biointerfaces. 2009;69(2):232–238. DOI: 10.1016/j.colsurfb.2008.11.033.Nogueira E., Gomes A. C., Preto A., Cavaco-Paulo A. Design of liposomal formulations for cell targeting. Colloids and Surfaces B: Biointerfaces. 2015;136:514–526. DOI: 10.1016/j.colsurfb.2015.09.034.Nogueira E., Gomes A. C., Preto A., Cavaco-Paulo A. Design of liposomal formulations for cell targeting. Colloids and Surfaces B: Biointerfaces. 2015;136:514–526. DOI: 10.1016/j.colsurfb.2015.09.034.Mali A. D., Bathe R. S. An updated review on liposome drug delivery system. Asian Journal of Pharmaceutical Research. 2015;5(3):151–157. DOI: 10.5958/2231-5691.2015.00023.4.Mali A. D., Bathe R. S. An updated review on liposome drug delivery system. Asian Journal of Pharmaceutical Research. 2015;5(3):151–157. DOI: 10.5958/2231-5691.2015.00023.4.Tam Y., Chen S., Cullis P. Advances in lipid nanoparticles for siRNA delivery. Pharmaceutics. 2013;5(3):498–507. DOI: 10.3390/pharmaceutics5030498.Tam Y., Chen S., Cullis P. Advances in lipid nanoparticles for siRNA delivery. Pharmaceutics. 2013;5(3):498–507. DOI: 10.3390/pharmaceutics5030498.Pastore M. N., Kalia Y. N., Horstmann M., Roberts M. S. Transdermal patches: history, development and pharmacology. British Journal of Pharmacology. 2015;172(9);2179–2209. DOI: 10.1111/bph.13059.Pastore M. N., Kalia Y. N., Horstmann M., Roberts M. S. Transdermal patches: history, development and pharmacology. British Journal of Pharmacology. 2015;172(9);2179–2209. DOI: 10.1111/bph.13059.Damnjanović J, Nakano H., Iwasaki Y. Simple and efficient profiling of phospholipids in phospholipase D-modified soy lecithin by HPLC with charged aerosol detection. Journal of the American Oil Chemists’ Society. 2013;90:951–957. DOI: 10.1007/s11746-013-2236-x.Damnjanović J, Nakano H., Iwasaki Y. Simple and efficient profiling of phospholipids in phospholipase D-modified soy lecithin by HPLC with charged aerosol detection. Journal of the American Oil Chemists’ Society. 2013;90:951–957. DOI: 10.1007/s11746-013-2236-x.Shirane D., Tanaka H., Nakai Y., Yoshioka H., Akita H. Development of an alcohol dilution–lyophilization method for preparing lipid nanoparticles containing encapsulated siRNA. Biological and Pharmaceutical Bulletin. 2018;41(8):1291–1294. DOI: 10.1248/bpb.b18-00208.Shirane D., Tanaka H., Nakai Y., Yoshioka H., Akita H. Development of an alcohol dilution–lyophilization method for preparing lipid nanoparticles containing encapsulated siRNA. Biological and Pharmaceutical Bulletin. 2018;41(8):1291–1294. DOI: 10.1248/bpb.b18-00208.Schoenmaker L., Witzigmann D., Kulkarni J. A., Verbeke R., Kersten G., Jiskoot W., Crommelin D. J. A. mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability. International Journal of Pharmaceutics. 2021;601:120586. DOI: 10.1016/j.ijpharm.2021.120586.Schoenmaker L., Witzigmann D., Kulkarni J. A., Verbeke R., Kersten G., Jiskoot W., Crommelin D. J. A. mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability. International Journal of Pharmaceutics. 2021;601:120586. DOI: 10.1016/j.ijpharm.2021.120586.Smith M. C., Crist R. M., Clogston J. D., McNeil S. E. Zeta potential: a case study of cationic, anionic, and neutral liposomes. Analytical and Bioanalytical Chemistry. 2017;409:5779–5787. DOI: 10.1007/s00216-017-0527-z.Smith M. C., Crist R. M., Clogston J. D., McNeil S. E. Zeta potential: a case study of cationic, anionic, and neutral liposomes. Analytical and Bioanalytical Chemistry. 2017;409:5779–5787. DOI: 10.1007/s00216-017-0527-z.Jiang G.-B., Quan D., Wang H., Liao K. Preparation of polymeric micelles based on chitosan bearing a small amount of highly hydrophobic groups. Carbohydrate Polymers. 2006;66(4):514–520.Jiang G.-B., Quan D., Wang H., Liao K. Preparation of polymeric micelles based on chitosan bearing a small amount of highly hydrophobic groups. Carbohydrate Polymers. 2006;66(4):514–520.Li J., Li Z., Zhou T., Zhang J., Xia H., Li H., He J., He S., Wang L. Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration. International Journal of Nanomedicine. 2015;10:6027–6037. DOI: 10.2147/IJN.S90347.Li J., Li Z., Zhou T., Zhang J., Xia H., Li H., He J., He S., Wang L. Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration. International Journal of Nanomedicine. 2015;10:6027–6037. DOI: 10.2147/IJN.S90347.Li J., Liang H., Liu J., Wang Z. Poly (amidoamine) (PAMAM) dendrimer mediated delivery of drug and pDNA/siRNA for cancer therapy. International Journal of Pharmaceutics. 2018;546(1–2):215–225. DOI: 10.1016/j.ijpharm.2018.05.045.Li J., Liang H., Liu J., Wang Z. Poly (amidoamine) (PAMAM) dendrimer mediated delivery of drug and pDNA/siRNA for cancer therapy. International Journal of Pharmaceutics. 2018;546(1–2):215–225. DOI: 10.1016/j.ijpharm.2018.05.045.Yellepeddi V. K., Ghandehari H. Poly(amido amine) dendrimers in oral delivery. Tissue Barriers. 2016;4(2):e1173773. DOI: 10.1080/21688370.2016.1173773.Yellepeddi V. K., Ghandehari H. Poly(amido amine) dendrimers in oral delivery. Tissue Barriers. 2016;4(2):e1173773. DOI: 10.1080/21688370.2016.1173773.Pires P. C., Mascarenhas-Melo F., Pedrosa K., Lopes D., Lopes J., Macário-Soares A., Peixoto D., Giram P. S., Veiga F., Paiva-Santos A. C. Polymer-based biomaterials for pharmaceutical and biomedical applications: A focus on topical drug administration. European Polymer Journal. 2023;187:111868. DOI: 10.1016/j.eurpolymj.2023.111868.Pires P. C., Mascarenhas-Melo F., Pedrosa K., Lopes D., Lopes J., Macário-Soares A., Peixoto D., Giram P. S., Veiga F., Paiva-Santos A. C. Polymer-based biomaterials for pharmaceutical and biomedical applications: A focus on topical drug administration. European Polymer Journal. 2023;187:111868. DOI: 10.1016/j.eurpolymj.2023.111868.Sharma R. Biodegradable Polymer Nanoparticles: Therapeutic Applications and Challenges. Oriental Journal Of Chemistry. 2022;38(6):1419–1427. DOI: 10.13005/ojc/380612.Sharma R. Biodegradable Polymer Nanoparticles: Therapeutic Applications and Challenges. Oriental Journal Of Chemistry. 2022;38(6):1419–1427. DOI: 10.13005/ojc/380612.Sung Y. K., Kim S. W. Recent advances in polymeric drug delivery systems. Biomaterials Research. 2020;24(1):12. DOI: 10.1186/s40824-020-00190-7.Sung Y. K., Kim S. W. Recent advances in polymeric drug delivery systems. Biomaterials Research. 2020;24(1):12. DOI: 10.1186/s40824-020-00190-7.Matalqah S. M., Aiedeh K., Mhaidat N. M., Alzoubi K. H., Bustanji Y., Hamad I. Chitosan nanoparticles as a novel drug delivery system: a review article. Current Drug Targets. 2020;21(15):1613–1624. DOI: 10.2174/1389450121666200711172536.Matalqah S. M., Aiedeh K., Mhaidat N. M., Alzoubi K. H., Bustanji Y., Hamad I. Chitosan nanoparticles as a novel drug delivery system: a review article. Current Drug Targets. 2020;21(15):1613–1624. DOI: 10.2174/1389450121666200711172536.Idrees H., Zaidi S. Z. J., Sabir A., Khan R. U., Zhang X., Hassan S. A review of biodegradable natural polymer-based nanoparticles for drug delivery applications. Nanomaterials. 2020;10(10):1970. DOI: 10.3390/nano10101970.Idrees H., Zaidi S. Z. J., Sabir A., Khan R. U., Zhang X., Hassan S. A review of biodegradable natural polymer-based nanoparticles for drug delivery applications. Nanomaterials. 2020;10(10):1970. DOI: 10.3390/nano10101970.Chen X., Han W., Wang G., Zhao X. Application prospect of polysaccharides in the development of anti-novel coronavirus drugs and vaccines. International Journal of Biological Macromolecules. 2020;164:331–343. DOI: 10.1016/j.ijbiomac.2020.07.106.Chen X., Han W., Wang G., Zhao X. Application prospect of polysaccharides in the development of anti-novel coronavirus drugs and vaccines. International Journal of Biological Macromolecules. 2020;164:331–343. DOI: 10.1016/j.ijbiomac.2020.07.106.Mandava K. Biological and non-biological synthesis of metallic nanoparticles: Scope for current pharmaceutical research. Indian Journal of Pharmaceutical Sciences. 2017;79(4):501–512.Mandava K. Biological and non-biological synthesis of metallic nanoparticles: Scope for current pharmaceutical research. Indian Journal of Pharmaceutical Sciences. 2017;79(4):501–512.Vangijzegem T., Stanicki D., Laurent S. Magnetic iron oxide nanoparticles for drug delivery: applications and characteristics. Expert Opinion on Drug Delivery. 2019;16(1):69–78. DOI: 10.1080/17425247.2019.1554647.Vangijzegem T., Stanicki D., Laurent S. Magnetic iron oxide nanoparticles for drug delivery: applications and characteristics. Expert Opinion on Drug Delivery. 2019;16(1):69–78. DOI: 10.1080/17425247.2019.1554647.Ojea-Jiménez I., Comenge J., García-Fernández L., Megson Z. A., Casals E., Puntes V. F. Engineered inorganic nanoparticles for drug delivery applications. Current Drug Metabolism. 2013;14(5):518–530. DOI: 10.2174/13892002113149990008.Ojea-Jiménez I., Comenge J., García-Fernández L., Megson Z. A., Casals E., Puntes V. F. Engineered inorganic nanoparticles for drug delivery applications. Current Drug Metabolism. 2013;14(5):518–530. DOI: 10.2174/13892002113149990008.Hu X., Zhang Y., Ding T., Liu J., Zhao H. Multifunctional gold nanoparticles: a novel nanomaterial for various medical applications and biological activities. Frontiers in Bioengineering and Biotechnology. 2020;8:990. DOI: 10.3389/fbioe.2020.00990.Hu X., Zhang Y., Ding T., Liu J., Zhao H. Multifunctional gold nanoparticles: a novel nanomaterial for various medical applications and biological activities. Frontiers in Bioengineering and Biotechnology. 2020;8:990. DOI: 10.3389/fbioe.2020.00990.Xie W., Guo Z., Gao F., Gao Q., Wang D., Liaw B.-S., Cai Q., Sun X., Wang X., Zhao L. Shape-, size- and structurecontrolled synthesis and biocompatibility of iron oxide nanoparticles for magnetic theranostics. Theranostics. 2018;8(12):3284–3307. DOI: 10.7150/thno.25220.Xie W., Guo Z., Gao F., Gao Q., Wang D., Liaw B.-S., Cai Q., Sun X., Wang X., Zhao L. Shape-, size- and structurecontrolled synthesis and biocompatibility of iron oxide nanoparticles for magnetic theranostics. Theranostics. 2018;8(12):3284–3307. DOI: 10.7150/thno.25220.Ries C. H., Cannarile M. A., Hoves S., Benz J., Wartha K., Runza V., Rey-Giraud F., Pradel L. P., Feuerhake F., Klaman I., Jones T., Jucknischke U., Scheiblich S., Kaluza K., Gorr I. H., Walz A., Abiraj K., Cassier P. A., Sica A., Gomez-Roca C., de Visser K. E., Italiano A., Le Tourneau C., Delord J.-P., Levitsky H., Blay J.-Y., Rüttinger D. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014;25(6):846–859. DOI: 10.1016/j.ccr.2014.05.016.Ries C. H., Cannarile M. A., Hoves S., Benz J., Wartha K., Runza V., Rey-Giraud F., Pradel L. P., Feuerhake F., Klaman I., Jones T., Jucknischke U., Scheiblich S., Kaluza K., Gorr I. H., Walz A., Abiraj K., Cassier P. A., Sica A., Gomez-Roca C., de Visser K. E., Italiano A., Le Tourneau C., Delord J.-P., Levitsky H., Blay J.-Y., Rüttinger D. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014;25(6):846–859. DOI: 10.1016/j.ccr.2014.05.016.Mitchell M. J., Billingsley M. M., Haley R. M., Wechsler M. E., Peppas N. A., Langer R. Engineering precision nanoparticles for drug delivery. Nature Reviews Drug Discovery. 2021;20(2):101–124. DOI: 10.1038/s41573-020-0090-8.Mitchell M. J., Billingsley M. M., Haley R. M., Wechsler M. E., Peppas N. A., Langer R. Engineering precision nanoparticles for drug delivery. Nature Reviews Drug Discovery. 2021;20(2):101–124. DOI: 10.1038/s41573-020-0090-8.Sterner R. C., Sterner R. M. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer Journal. 2021;11(4):69. DOI: 10.1038/s41408-021-00459-7.Sterner R. C., Sterner R. M. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer Journal. 2021;11(4):69. DOI: 10.1038/s41408-021-00459-7.Tam Y. Y. C., Chen S., Cullis P. R. Advances in lipid nanoparticles for siRNA delivery. Pharmaceutics. 2013;5(3):498–507. DOI:10.3390/pharmaceutics5030498.Tam Y. Y. C., Chen S., Cullis P. R. Advances in lipid nanoparticles for siRNA delivery. Pharmaceutics. 2013;5(3):498–507. DOI:10.3390/pharmaceutics5030498.Sydow K., Nikolenko H., Lorenz D., Müller R. H., Dathe M. Lipopeptide-based micellar and liposomal carriers: Influence of surface charge and particle size on cellular uptake into blood brain barrier cells. European Journal of Pharmaceutics and Biopharmaceutics. 2016;109:130–139. DOI: 10.1016/j.ejpb.2016.09.019.Sydow K., Nikolenko H., Lorenz D., Müller R. H., Dathe M. Lipopeptide-based micellar and liposomal carriers: Influence of surface charge and particle size on cellular uptake into blood brain barrier cells. European Journal of Pharmaceutics and Biopharmaceutics. 2016;109:130–139. DOI: 10.1016/j.ejpb.2016.09.019.Pozharitskaya O. N., Kozur Yu. M., Osochuk S. S., Flisyuk E. V., Smekhova I. E., Malkov S. D., Zarifi K. O., Titovich I. A., Krasova E. K., Shikov A. N. Liposomes – metabolically active drug transport systems: visualization and pharmacokinetic. Part 2 (review). Drug development & registration. 2024;13(4):78–98. (In Russ.) DOI: 10.33380/2305-2066-2024-13-4-1919.Pozharitskaya O. N., Kozur Yu. M., Osochuk S. S., Flisyuk E. V., Smekhova I. E., Malkov S. D., Zarifi K. O., Titovich I. A., Krasova E. K., Shikov A. N. Liposomes – metabolically active drug transport systems: visualization and pharmacokinetic. Part 2 (review). Drug development & registration. 2024;13(4):78–98. (In Russ.) DOI: 10.33380/2305-2066-2024-13-4-1919.Fischer K., Schmidt M. Pitfalls and novel applications of particle sizing by dynamic light scattering. Biomaterials. 2016;98:79–91. DOI: 10.1016/j.biomaterials.2016.05.003.Fischer K., Schmidt M. Pitfalls and novel applications of particle sizing by dynamic light scattering. Biomaterials. 2016;98:79–91. DOI: 10.1016/j.biomaterials.2016.05.003.Forero Ramirez L. M., Rihouey C., Chaubet F., Le Cerf D., Picton L. Characterization of dextran particle size: How frit-inlet asymmetrical flow field-flow fractionation (FI-AF4) coupled online with dynamic light scattering (DLS) leads to enhanced size distribution. Journal of Chromatography A. 2021;1653:462404. DOI: 10.1016/j.chroma.2021.462404.Forero Ramirez L. M., Rihouey C., Chaubet F., Le Cerf D., Picton L. Characterization of dextran particle size: How frit-inlet asymmetrical flow field-flow fractionation (FI-AF4) coupled online with dynamic light scattering (DLS) leads to enhanced size distribution. Journal of Chromatography A. 2021;1653:462404. DOI: 10.1016/j.chroma.2021.462404.Sitterberg J., Özcetin A., Ehrhardt C., Bakowsky U. Utilising atomic force microscopy for the characterisation of nanoscale drug delivery systems. European Journal of Pharmaceutics and Biopharmaceutics. 2010;74(1):2–13. DOI: 10.1016/j.ejpb.2009.09.005.Sitterberg J., Özcetin A., Ehrhardt C., Bakowsky U. Utilising atomic force microscopy for the characterisation of nanoscale drug delivery systems. European Journal of Pharmaceutics and Biopharmaceutics. 2010;74(1):2–13. DOI: 10.1016/j.ejpb.2009.09.005.Akhtar K., Khan S. A., Khan S. B., Asiri A. M. Scanning electron microscopy: Principle and applications in nanomaterials characterization. In: Sharma S. K., editor. Handbook of Materials Characterization. Cham: Springer; 2018. P. 113–145. DOI: 10.1007/978-3-319-92955-2_4.Akhtar K., Khan S. A., Khan S. B., Asiri A. M. Scanning electron microscopy: Principle and applications in nanomaterials characterization. In: Sharma S. K., editor. Handbook of Materials Characterization. Cham: Springer; 2018. P. 113–145. DOI: 10.1007/978-3-319-92955-2_4.Yang Y., Chen Y., Li D., Lin S., Chen H., Wu W., Zhang W. Linolenic acid conjugated chitosan micelles for improving the oral absorption of doxorubicin via fatty acid transporter. Carbohydrate Polymers. 2023;300:120233. DOI: 10.1016/j.carbpol.2022.120233.Yang Y., Chen Y., Li D., Lin S., Chen H., Wu W., Zhang W. Linolenic acid conjugated chitosan micelles for improving the oral absorption of doxorubicin via fatty acid transporter. Carbohydrate Polymers. 2023;300:120233. DOI: 10.1016/j.carbpol.2022.120233.Dehghani B., Mirzaei M., Lohrasbi-Nejad A. Characterization of Thermoresponsive Poly(N-vinylcaprolactam) Polymer Containing Doxorubicin-Loaded Niosomes: Synthesis, Structural Properties, and Anticancer Efficacy. Journal of Pharmaceutical Innovation. 2025;20(1):7.Dehghani B., Mirzaei M., Lohrasbi-Nejad A. Characterization of Thermoresponsive Poly(N-vinylcaprolactam) Polymer Containing Doxorubicin-Loaded Niosomes: Synthesis, Structural Properties, and Anticancer Efficacy. Journal of Pharmaceutical Innovation. 2025;20(1):7.Silva K. C., Corio P., Santos J. J. Characterization of the chemical interaction between single-walled carbon nanotubes and titanium dioxide nanoparticles by thermogravimetric analyses and resonance Raman spectroscopy. Vibrational Spectroscopy. 2016;86:103–108.Silva K. C., Corio P., Santos J. J. Characterization of the chemical interaction between single-walled carbon nanotubes and titanium dioxide nanoparticles by thermogravimetric analyses and resonance Raman spectroscopy. Vibrational Spectroscopy. 2016;86:103–108.Xiong X., Wang Y., Zou W., Duan J., Chen Y. Preparation and characterization of magnetic chitosan microcapsules. Journal of Chemistry. 2013;2013:585613. DOI: 10.1155/2013/585613.Xiong X., Wang Y., Zou W., Duan J., Chen Y. Preparation and characterization of magnetic chitosan microcapsules. Journal of Chemistry. 2013;2013:585613. DOI: 10.1155/2013/585613.Luo G., Yang Q., Yao B., Tian Y., Hou R., Shao A., Li M., Feng Z., Wang W. Slp-coated liposomes for drug delivery and biomedical applications: potential and challenges. International Journal of Nanomedicine. 2019;14:1359–1383. DOI: 10.2147/IJN.S189935.Luo G., Yang Q., Yao B., Tian Y., Hou R., Shao A., Li M., Feng Z., Wang W. Slp-coated liposomes for drug delivery and biomedical applications: potential and challenges. International Journal of Nanomedicine. 2019;14:1359–1383. DOI: 10.2147/IJN.S189935.Li Y., Driver M., Decker E., He L. Lipid and lipid oxidation analysis using surface enhanced Raman spectroscopy (SERS) coupled with silver dendrites. Food Research International. 2014;58:1–6. DOI: 10.1016/j.foodres.2014.01.056.Li Y., Driver M., Decker E., He L. Lipid and lipid oxidation analysis using surface enhanced Raman spectroscopy (SERS) coupled with silver dendrites. Food Research International. 2014;58:1–6. DOI: 10.1016/j.foodres.2014.01.056.Jangle R. D., Galge R. V., Patil V. V., Thorat B. N. Selective HPLC method development for soy phosphatidylcholine fatty acids and its mass spectrometry. Indian Journal of Pharmaceutical Sciences. 2013;75(3):339–345. DOI: 10.4103/0250-474X.117435.Jangle R. D., Galge R. V., Patil V. V., Thorat B. N. Selective HPLC method development for soy phosphatidylcholine fatty acids and its mass spectrometry. Indian Journal of Pharmaceutical Sciences. 2013;75(3):339–345. DOI: 10.4103/0250-474X.117435.Singh R., Bharti N., Madan J., Hiremath S. N. A rapid isocratic high-performance liquid chromatography method for determination of cholesterol and 1,2-dioleoyl-sn-glycero-3-phosphocholine in liposome-based drug formulations. Journal of Chromatography A. 2015;1073(1–2):347–353.Singh R., Bharti N., Madan J., Hiremath S. N. A rapid isocratic high-performance liquid chromatography method for determination of cholesterol and 1,2-dioleoyl-sn-glycero-3-phosphocholine in liposome-based drug formulations. Journal of Chromatography A. 2015;1073(1–2):347–353.Son H.-H., Moon J.-Y., Seo H. S., Kim H. H., Chung B. C., Choi M. H. High-temperature GC-MS-based serum cholesterol signatures may reveal sex differences in vasospastic angina. Journal of Lipid Research. 2014;55(1):155–162. DOI: 10.1194/jlr.D040790.Son H.-H., Moon J.-Y., Seo H. S., Kim H. H., Chung B. C., Choi M. H. High-temperature GC-MS-based serum cholesterol signatures may reveal sex differences in vasospastic angina. Journal of Lipid Research. 2014;55(1):155–162. DOI: 10.1194/jlr.D040790.Scherer M., Böttcher A., Liebisch G. Lipid profiling of lipoproteins by electrospray ionization tandem mass spectrometry. Biochimica et Biophysica Acta (BBA) – Molecular and Cell Biology of Lipids. 2011;1811(11):918–924. DOI: 10.1016/j.bbalip.2011.06.016.Scherer M., Böttcher A., Liebisch G. Lipid profiling of lipoproteins by electrospray ionization tandem mass spectrometry. Biochimica et Biophysica Acta (BBA) – Molecular and Cell Biology of Lipids. 2011;1811(11):918–924. DOI: 10.1016/j.bbalip.2011.06.016.Marifova Z. A., Azizov I. K. Determination of phosphatidylcholine and α-tocopherol in the seed oil from black cumin (Nigella sativa l.) growing in Uzbekistan. Pharmacy. 2018;67(1):19–23. (Russ.) DOI: 10.29296/25419218-2018-01-04.Marifova Z. A., Azizov I. K. Determination of phosphatidylcholine and α-tocopherol in the seed oil from black cumin (Nigella sativa l.) growing in Uzbekistan. Pharmacy. 2018;67(1):19–23. (Russ.) DOI: 10.29296/25419218-2018-01-04.Paulazo M. A., Sodero A. O. Analysis of cholesterol in mouse brain by HPLC with UV detection. PLOS One. 2020;15(1):e0228170. DOI: 10.1371/journal.pone.0228170.Paulazo M. A., Sodero A. O. Analysis of cholesterol in mouse brain by HPLC with UV detection. PLOS One. 2020;15(1):e0228170. DOI: 10.1371/journal.pone.0228170.Kolarič L., Šimko P. Determination of cholesterol content in butter by HPLC: Up-to-date optimization, and in-house validation using reference materials. Foods. 2020;9(10):1378. DOI: 10.3390/foods9101378.Kolarič L., Šimko P. Determination of cholesterol content in butter by HPLC: Up-to-date optimization, and in-house validation using reference materials. Foods. 2020;9(10):1378. DOI: 10.3390/foods9101378.Jing Z., Xianmei H., Tianxin W., Hao L., Qipeng Y. HPLC analysis of egg yolk phosphatidylcholine by evaporative light scattering detector. Chinese Journal of Chemical Engineering. 2012;20(4):665–672.Jing Z., Xianmei H., Tianxin W., Hao L., Qipeng Y. HPLC analysis of egg yolk phosphatidylcholine by evaporative light scattering detector. Chinese Journal of Chemical Engineering. 2012;20(4):665–672.Bender V., Fuchs L., Süss R. RP-HPLC-CAD method for the rapid analysis of lipids used in lipid nanoparticles derived from dual centrifugation. International Journal of Pharmaceutics: X. 2024;7:100255. DOI: 10.1016/j.ijpx.2024.100255.Bender V., Fuchs L., Süss R. RP-HPLC-CAD method for the rapid analysis of lipids used in lipid nanoparticles derived from dual centrifugation. International Journal of Pharmaceutics: X. 2024;7:100255. DOI: 10.1016/j.ijpx.2024.100255.

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