Development of a model composition of the liposomal form of gefitinib

DOI: https://doi.org/10.29296/25419218-2023-02-03
Issue: 
2
Year: 
2023

N.I. Burdaev(1), L.L. Nikolaeva(2, 3), Z.S. Shprakh(2, 3), N.D. Bunyatyan(1, 2), A.V. Lantsova(2), E.V. Sanarova(2), V.V. Kosenko(1)
1-Scientific Centre for Expert Evaluation of Medicinal Products, Petrovsky boulevard 8, bld. 2, Moscow, 127051, Russian Federation;
2-N.N. Blokhin National Medical Research Center of Oncology, Kashirskoye sh., 24, Moscow, 115478, Russian Federation;
3-I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University), Trubetskaya St., bld. 2, 8, Moscow, 119991, Russian Federation

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.
Keywords: 
gefetinib
liposomes
vesicles
phosphatidylcholine
cryoprotectant
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