RESEARH OF THE LIPID MEMBRANE COMPOSITION DURING LIPOSOMAL IRINOTECAN CREATION
DOI:
https://doi.org/10.11603/2312-0967.2017.1.7557Keywords:
liposomes, Irinotecan, lipid bilayer, phosphatidylcholine, cholesterol, high pressure homogenization.Abstract
The aim of the work. Research the effect of lipid membrane composition on the encapsulation degree and the size of nanoparticles in the pharmaceutical development of liposomal irinotecan.
Materials and Methods. Reagents were purchased from Lipoid, Germany and Sigma-Aldrich, USA. The following instruments were used: Buchi 210, Zetasizer Nano ZS, Minim2 with cassettes with an upper cut-off limit of 30 kDa, Shimadzu LC-20 HPLC. Liposomes with irinotecan were obtained by the "chemical gradient" technology.
Results and Discussion. For purposes of liposomal irinotecan creation, lipid membranes with different phosphatidylcholine/cholesterol ratio were studied. It was determined that increasing of the cholesterol weight ratio in the membrane, improves the encapsulation of irinotecan when a «chemical gradient» method was used. On the other hand, at a mass ratio of phosphatidylcholine / cholesterol 75/25 and 70/30 it was impossible to avoid particles larger than 1000 nm formation, that is unacceptable from the position of industrial technology application.
Conclusions. An experiment was performed to research the optimal composition of the lipid membrane using three types of cryoprotectants. It was studied the in uence of liposomal membranes with the ratio of lipids phosphatidylcholine/cholesterol: 85/15; 80/20; 75/25; 70/30 on liposomes size and encapsulation degree. The ratio of 80/20 was de ned as optimum for obtaining liposomes with irinotecan. Ways of improving of irinotecan encapsulation into liposomes were outlined.
References
Sessa G, Weissmann G. Phospholipid spherules (liposomes) as a model for biological membranes. J Lipid Res. 1968; 9(3): 310-318.
Madni A, Sarfraz M, Rehman M, Ahmad M, Akhtar N, Ahmad S et al. Liposomal drug delivery: a versatile platform for challenging clinical applications. J Pharm Pharm Sci. 2014;17(3): 401-26. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25224351
Shvets VI. Liposomalnaya platforma dlya sozdaniya nizkotoksichnikh protivoopuholevih preparatov. Vestnik MITHT. 2014;4: 4-25; Russian.
Shahmaev AY, Katsai AL, Prohorov VV, Stadnichenko AV, Balabanyan VY, Krasnopolskiy YM et al. Investigation of the methods of inclusion of medicinal substances in liposomal nanoparticles. Remedium. 2015;12: 26-59. Available from:http://elibrary.ru/item.asp?id=25280721; Russian.
Dudnichenko AV, Krasnopolskiy YM, Shvets VI. Liposomal drugs in the experiment and clinic. [Липосомальные лекарственные препараты в эксперименте и клинике] Kharkov: RA-Karavella; 2001. Russian.
Rahman YE, Hanson WR, Bharucha J, Ainsworth EJ, Jaroslow BN. Mechanisms of reduction of antitumor drug toxicity by liposome encapsulation. Ann. N. Y. Acad Sci. 1978;308: 325-42. Available from: https://www.ncbi.nlm.nih.gov/pubmed/279296
Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Research. 1986;46: 6387-92. Available from: https://www.ncbi.nlm.nih.gov/pubmed/2946403
Stadnichenko AV, Krasnopolskiy YM, Shvets VI. The technology of obtaining liposomal forms of irinotecan (review). Biofarmacevtichesky zhurnal. 2014;6(6): 3-9. Available from: http://www.biopharmj.ru/ojs238/index.php/biopharmj/article/view/249
Ofcial FDA site. FDA prescribing information. Irinotecan. 2010. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020571s048lbl.pdf
Paulіk A, Grim J, Filip S. Predictors of Irinotecan toxicity and efficacy in treatment of metastatic colorectal cancer. Acta Medica. 2012;55(4): 153-59. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23631285
Kopjar N, Zeljezic D, Vrdoljak A. Irinotecan Toxicity to Human Blood Cells in vitro: Relationship between Various Biomarkers. Basic and Clinical Pharmacology and Toxicology. 2007;100(6): 403-13. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17516995
Stadnichenko AV, Krasnopolskiy YM, Shvets VI. Development and validation of the procedure for determining the degree of encapsulation of irinotecan hydrochloride in liposomes. Biofarmacevtichesky zhurnal. 2015;7(1): 53-55. Available from: http://elibrary.ru/item.asp?id=23787998.
Li J, Wang X, Zhang T. A review on phospholipids and their main applications in drug delivery systems. Asian journal of pharmaceutical sciences. 2014;1: 1-18. Available from: http://www.sciencedirect.com /science/article/pii/S1818087614000725
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