Validation of a UV-Spectrophotometric Method for Quantitative Determination of Paclitaxel in a Targeted Delivery System
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Pharmaceutical Chemistry Journal, Vol. 54, No. 8, November, 2020 (Russian Original Vol. 54, No. 8, August, 2020)
VALIDATION OF A UV-SPECTROPHOTOMETRIC METHOD FOR QUANTITATIVE DETERMINATION OF PACLITAXEL IN A TARGETED DELIVERY SYSTEM BASED ON POLY(LACTIC–GLYCOLIC ACID) COPOLYMER NANOPARTICLES M. B. Sokol,1,2,* Yu. V. Sycheva,1 N. G. Yabbarov,1,2 A. I. Zabolotskii,1,3 M. D. Mollaev,1,4 M. R. Faustova,1,2,4 O. G. Tereshchenko,1 M. V. Fomicheva,1,2 and E. D. Nikol’skaya1,2 Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 54, No. 8, pp. 47 – 51, August, 2020.
Original article submitted January 23, 2020. A UV spectrophotometric method for quantitative determination of paclitaxel in a conjugate of poly(lactic-glycolic acid) (PLGA) copolymer nanoparticles and a protein vector (recombinant third domain of alpha-fetoprotein) was developed. Paclitaxel was determined at wavelength 260 ± 2 nm. The proposed method showed specificity, linearity (R2 = 0.9948) in the range 80 – 120% of paclitaxel nominal load in the polymer matrix (0.18 mg/mL), accuracy, and precision. The developed method could be recommended for inclusion in regulatory documentation for quality control of paclitaxel nanoparticles conjugated with a protein vector. Keywords: paclitaxel, PLGA, recombinant alpha-fetoprotein, validation, UV spectrophotometry.
The commercial preparation of Ptx, i.e., Taxol®, is supplied as a micellar dispersion of Ptx in EtOH and Cremophor EL because of the low water-solubility of Ptx (0.7 mg/mL). Use of Taxol® is limited because of allergic reactions and nephro- and neurotoxicity [3]. Moreover, the in vivo biodistribution of Ptx is nonspecific so that its general toxicity is increased and side effects arise [3]. Encapsulation of hydrophobic drugs in poly(lactic-glycolic acid) (PLGA) copolymer nanoparticles can boost their bioavailability and prolong their release. Construction of targeted delivery systems, e.g., conjugates of polymer particles with vector molecules, promotes their selective accumulation in organs and target tissues and also increases the specificity of hydrophobic antitumor drugs. A method for preparing a targeted delivery system for Ptx as a conjugate of PLGA nanoparticles containing Ptx with the recombinant third domain of alpha-fetoprotein (AFT) (NP–rAFT3d) was developed in the Department of Biomedicinal Chemistry, Russian Research Center for Molecular Diagnosis and Treatment (VNTsMDL). AFP is a human oncofetal protein that is currently used as a specific
Paclitaxel (Ptx) is a plant-based mitotic inhibitor that is used for chemotherapy of patients with malignant neoplasms. The mechanism of action of paclitaxel is related to its effect on cell division. The drug stimulates assembly of microtubules from tubulin dimers and stabilizes them by suppressing depolymerization. This action disrupts the normal dynamic rearrangement of the microtubule network, which is important for cellular functions during cell-cycle mitosis and interphase stages [1]. Paclitaxel is classified as a taxane and diterpenoid pseudoalk
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