Development of a model composition of the liposomal form of gefitinib
- Authors: Burdaev N.I.1, Nikolaeva L.L.2,3, Shprakh Z.S.2,3, Bunyatyan N.D.1,4, Lantsova A.V.2, Sanarova E.V.2, Kosenko V.V.1
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Affiliations:
- Scientific Centre for Expert Evaluation of Medicinal Products
- N.N. Blokhin National Medical Research Center of Oncology
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University)
- 2N.N. Blokhin National Medical Research Center of Oncology
- Issue: Vol 72, No 2 (2023)
- Pages: 17-21
- Section: Technology of medicines
- URL: https://journals.eco-vector.com/0367-3014/article/view/321898
- DOI: https://doi.org/10.29296/25419218-2023-02-03
- ID: 321898
Cite item
Open Access
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Abstract
Introduction. One of the promising directions in the development of anticancer therapy is the creation of controlled release delivery systems. Modern anticancer drugs, despite their targeted action, have an insufficiently high affinity for the tumor, in addition, most of them are administered orally, and therefore have low bioavailability, so research in the field of creating targeted drugs with controlled release is relevant and promising.
Objective: to develop the composition and technology for obtaining the liposomal form of gefitinib.
Material and methods. Liposomes were obtained by the Bengham method with a modification for hydrophobic substances. The analysis of the obtained liposomes was carried out using spectrophotometry, laser scattering spectroscopy, a method for determining the electrophoretic mobility of particles, and viscometry.
Results. On the basis of lipid components and active substance in various molar ratios, compositions were made and experimental models of liposomal dispersion were obtained. The formulations were evaluated for efficiency of incorporation of gefitinib into vesicles and size. As a result of the analysis of 6 studied formulations, the optimal mass ratios of the components of the dosage form were determined – gefitinib/phosphatidylcholine 1:187.5 and phosphatidylcholine/cholesterol/pegylated phoosphatidylcholine 83.33/6.67/1. The use of this composition makes it possible to obtain uniform sized liposomes with a diameter of about 190 nm. To increase the stability and increase the shelf life, lyophilization was carried out, and sucrose was introduced into the model as a cryoprotectant.
Conclusion. Based on the results of a number of technological and chemical-pharmaceutical studies, the model composition of the liposomal dosage form of the targeted compound gefitinib was selected.
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About the authors
Nikolai I. Burdaev
Scientific Centre for Expert Evaluation of Medicinal Products
Email: burd.mobile@gmail.com
ORCID iD: 0000-0003-0662-495X
expert of the 2nd category of the laboratory of chemical and pharmaceutical substances
Russian Federation, Petrovsky boulevard 8, bld. 2, Moscow, 127051Lyudmila L. Nikolaeva
N.N. Blokhin National Medical Research Center of Oncology; I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University)
Email: alima91@yandex.ru
ORCID iD: 0000-0001-8003-8241
Ph.D. in Pharmaceutical Sciences, Researcher, Laboratory for the Development of Dosage Forms, Associate Professor, Department of Pharmaceutical Technology and Pharmacology
Russian Federation, Trubetskaya St., bld. 2, 8, Moscow, 119991; Kashirskoye sh., 24, Moscow, 115478Zoya S. Shprakh
N.N. Blokhin National Medical Research Center of Oncology; I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University)
Email: z.shprakh@ronc.ru
ORCID iD: 0000-0003-3034-750X
Doctor of Pharmaceutical Sciences, Acting Head of the Laboratory of Chemical and Pharmaceutical Analysis, Associate Professor, Department of Pharmaceutical Technology and Pharmacology
Russian Federation, Trubetskaya St., bld. 2, 8, Moscow, 119991; Kashirskoye sh., 24, Moscow, 115478Natalia D. Bunyatyan
Scientific Centre for Expert Evaluation of Medicinal Products; 2N.N. Blokhin National Medical Research Center of Oncology
Email: Bunyatyan@expmed.ru
ORCID iD: 0000-0003-0936-5551
Doctor of Pharmaceutical Sciences, Professor, Chief Analyst of the Center for Clinical Pharmacology, Head of the Department of Pharmaceutical Technology and Pharmacology
Russian Federation, Petrovsky boulevard 8, bld. 2, Moscow, 127051; Kashirskoye sh., 24, Moscow, 115478Anna V. Lantsova
N.N. Blokhin National Medical Research Center of Oncology
Author for correspondence.
Email: lantsova1979@mail.ru
ORCID iD: 0000-0002-0650-2023
Ph.D. in Pharmaceutical Sciences, Leading Researcher, Laboratory for the Development of Dosage Forms
Russian Federation, Kashirskoye sh., 24, Moscow, 115478Ekaterina V. Sanarova
N.N. Blokhin National Medical Research Center of Oncology
Email: sanarova8686@mail.ru
ORCID iD: 0000-0002-5592-5137
Ph.D. in Pharmaceutical Sciences, Senior Researcher, Laboratory for the Development of Dosage Forms
Russian Federation, Kashirskoye sh., 24, Moscow, 115478Valentina V. Kosenko
Scientific Centre for Expert Evaluation of Medicinal Products
Email: general@expmed.ru
ORCID iD: 0000-0001-8353-7863
Ph.D. in Pharmaceutical Sciences, General Director
Russian Federation, Petrovsky boulevard 8, bld. 2, Moscow, 127051References
- Tong C.W.S., Wu W.K.K., Loong H.H.F., Cho W.C.S., To K.K.W. Drug combination approach to overcome resistance to EGFR tyrosine kinase inhibitors in lung cancer. Cancer Letters. 2017; 405: 100–10. doi: 10.1016/j.canlet.2017.07.023
- Zhou X., Shi K., Hao Y., Yang C., Zha R., Yi C., Qian Z. Advances in nanotechnology-based delivery systems for EGFR tyrosine kinases inhibitors in cancer therapy. Asian Journal of Pharmaceutical Sciences. 2020; 15 (1): 26–41. doi: 10.1016/j.ajps.2019.06.001
- Тишков С.В., Блынская Е.В., Алексеев К.В., Юдина Д.В. Разработка состава и технологии таблеток гефитиниба. Современные тенденции развития науки и технологий. 2016; 9–3: 41–3. [Tishkov S.V., Blynskaya E.V., Alekseev K.V., Yudina D.V. Development of the composition and technology of gefitinib tablets. Modern trends in the development of science and technology. 2016; 9–3: 41–3 (in Russian)].
- Rohilla S., Awasthi R., Mehta M., Chellappan D.K., Gupta G., Gulati M., Singh S.K., Anand K., Oliver B.G., Dua K., Dureja H. Preparation and Evaluation of Gefitinib Containing Nanoliposomal Formulation for Lung Cancer Therapy. BioNanoSci. 2022; 12: 241–55. doi: 10.1007/s12668-022-00938-6
- Akshat S., Asha P., Abhay D. Optimization of Solid Lipid Nanoparticles and Nanostructured Lipidic Carriers as Promising Delivery for Gefitinib: Characterization and Invitro Evaluation, Current Drug Therapy. 2021; 16 (2): 170–83. doi: 10.2174/1574885516666210125111945
- Лугэнь Б., Дмитриева М.В., Орлова О.Л., Краснюк И.И., Краснюк И.И. (мл.), Боков Д.О., Степанова О.И., Беляцкая А.В. Разработка состава липосомальной лекарственной формы гидрофобного производного индолокарбазола. Разработка и регистрация лекарственных средств. 2020; 9 (3): 21–6. doi: 10.33380/2305-2066-2020-9-3-21-26 [Lugen B., Dmitrieva M.V., Orlova O.L., Krasnyuk I.I., Krasnyuk I.I. (jr.), Bokov D.O., Stepanova O.I., Belyackaya A.V. Development of a liposomal dosage form based on hydrophobic derivative of indolocarbazole. Razrabotka i registratsiya lekarstvennykh sredstv = Drug development & registration. 2020; 9 (3): 21–6. doi: 10.33380/2305-2066-2020-9-3-21-26 (in Russian)].
- Sanarova E.V., Lantsova A.V., Polozkova A.P., Orlova O.L., Meerovich I.G., Borisova L.M., Kiseleva M.P., Smirnova Z.S., Kul’bachevskaya N.Y., Konyaeva O.I., Oborotova N.A. Effectiveness of liposomal system of delivery of hydrophobic antineoplastic thiosens photosensitizer. Nanotechnologies in Russia. 2015; 10 (5–6): 492–500. doi: 10.1134/S1995078015030143.
- Гулякин И.Д., Хашем А., Николаева Л.Л., Дмитриева М.В., Афанасьева Д.А., Барышникова М.А., Оборотова Н.А., Ланцова А.В. Разработка новой технологии получения лекарственной формы для внутривенного введения производного индолокарбазола ЛХС-1208. Российский биотерапевтический журнал. 2016; 15 (2): 55–60. doi: 10.17650/1726-9784-2016-15-2-55-60 [Gulyakin I.D., Hashem A., Nikolaeva L.L., Dmitrieva M.V., Afanasieva D.A., Baryshnikova M.A., Oborotova N.A., Lantsova A.V. The development of new technology of the dosage form for intravenous administration indolocarbazole derivative LHS-1208. Russian Journal of Biotherapy. 2016; 15 (2): 55–60. doi: 10.17650/1726-9784-2016-15-2-55-60 (in Russian)].
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