Standardization of paclitaxel formulation consisting of a conjugate of polymer nanoparticles with a protein vector molecule

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 protein 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 "Biotechnological drugs". Results. The quality assessment of Ptx formulation was proposed according to the following attributes: "Particle size" (250-300 nm), "pH of the suspension" (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 concentration 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.

PLGA, paclitaxel, standardization, PLGA, alpha-fetoprotein, nanoparticles