STANDARDIZATION OF PACLITAXEL FORMULATION CONSISTING OF A CONJUGATE OF POLYMER NANOPARTICLES WITH A PROTEIN VECTOR MOLECULE

DOI: https://doi.org/10.29296/25877313-2021-07-03
Issue: 
7
Year: 
2021

M.B. Sokol Junior Research Scientist, Institute of Biochemical Physics named after N.M. Emanuel of Russian Academy of Sciences; Russian Research Center for Molecular Diagnostics and Therapy (Moscow, Russia) E-mail: mariyabsokol@gmail.com N.G. Yabbarov Ph.D. (Biol.), Institute of Biochemical Physics named after N.M. Emanuel of Russian Academy of Sciences; Russian Research Center for Molecular Diagnostics and Therapy (Moscow, Russia) M.R. Mollaeva Post-graduate Student, Institute of Biochemical Physics named after N.M. Emanuel of Russian Academy of Sciences; Russian Research Center for Molecular Diagnostics and Therapy (Moscow, Russia) M.V. Fomicheva Junior Research Scientist, Institute of Biochemical Physics named after N.M. Emanuel of Russian Academy of Sciences; Russian Research Center for Molecular Diagnostics and Therapy (Moscow, Russia) V.Yu. Balaban’yan Dr.Sc. (Pharm.), Lomonosov Moscow State University (Moscow, Russia) E.D. Nikolskaya Ph.D. (Chem.), Institute of Biochemical Physics named after N.M. Emanuel of Russian Academy of Sciences; Russian Research Center for Molecular Diagnostics and Therapy (Moscow, Russia)

Relevance. A chemotherapeutic agentpaclitaxel (Ptx) has limited usage because of the pronounced side effects of excipients and the non-specificity of Ptx action. We proposed a novel Ptx formulation for targeted therapy of malignant neoplasms and reducing the level of side effects. Aim of the study was to develop a normative documentation for standardization of a novel Ptx formulation consisting of a polymer matrix and a pro-tein vector molecule. Material and methods. When compiling the normative documentation, we were guided by GPM.1.4.1.0007.15 of The State Pharmacopoeia of the Russian Federation XIV "Dosage forms for parenteral use" and GPM.1.7.1.0011.18 of The State Pharmacopoeia of the Russian Federation XIV "Biotech-nological drugs". Results. The quality assessment of Ptx formulation was proposed according to the following attributes: "Particle size" (250–300 nm), "pH of the sus-pension" (5.8–7.6), "Reconstitution time" (no more than 15 min), "Passage of the suspension through the needle", "Sedimentation stability" (not less than 4 h), "Water content" (no more than 3%), "Mechanical inclusions", "Identity" and "Quantification" (paclitaxel concentration not less than 4.5% and no more than 5.5%), "Purity" (not less than 95%), "Organic impurities" (no more than 3.7%), "Residual organic solvents" (methylene chloride concen-tration no more than 0.06%), "Elemental impurities" (tin concentration not more than 640 ppm),"Uniformity of mass" (deviation from the average mass no more than 10%)," Residual DNA" (no more than 10 pg/mg), "Bacterial endotoxins" (no more than 0.25), "Sterility". Conclusions. Quality control parameters were proposed to ensure the safety and efficacy of the original FPP for anticancer therapy

Keywords: 
paclitaxel
standardization
PLGA
alpha-fetoprotein
nanoparticles

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