Development of Docetaxel-loaded Folate-modified Poly(lactic-co-glycolic acid) Particles

authors:

avatar Yuri Poltavets 1 , * , avatar Vasilisa V. Zavarzina 1 , avatar Sergey L. Kuznetsov 1 , avatar Anna A. Krasheninnikova 1 , avatar Danil O. Dronov 1 , avatar Nadezhda V. Gukasova 1 , avatar Valentina G. Shuvatova 1 , avatar Vadim Yu. Balabanyan 2

Laboratory of Nanocapsules and Targeted Delivery of Drugs, National Research Centre “Kurchatov Institute”, Moscow, Russia
Department of Pharmaceutical technology, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia
Journal of Reports in Pharmaceutical Sciences: Vol.8, issue 2; 253-61
published online: December 31, 2019
article type: Research Article
DOI: https://doi.org/10.4103/jrptps.JRPTPS_64_19

how to cite: Poltavets Y, Zavarzina V V, Kuznetsov S L, Krasheninnikova A A, Dronov D O, et al. Development of Docetaxel-loaded Folate-modified Poly(lactic-co-glycolic acid) Particles. J Rep Pharm Sci. 2019;8(2):e147389. https://doi.org/10.4103/jrptps.JRPTPS_64_19.

Abstract

Background: Poly(lactic-co-glycolic acid) (PLGA) particles with small vector molecules are used for targeted delivery of anticancer agents. To be effective, they must be small, noncytotoxic, sterile, and stable. 
Aim: The aim of this study was to prepare docetaxel-loaded folate-modified PLGA-based nanoparticles (FD-Dtx-NPs) and to assess their as parenteral folate-receptor targeted delivery systems during γ-sterilization and long-term storage. 
Materials and Methods: NPs were prepared by oil/water single emulsion-solvent evaporation method and simultaneous loading of polymer particles with docetaxel and folic acid derivative. NPs’ physicochemical characteristics and antitumor activity were assessed. 
Findings: FD-Dtx-NPs presented uniform characteristics over repeated measurements: ~250 nm size, <0.100 polydispersity index, and >2.5% docetaxel content in the finished lyophilizate. The observed slow docetaxel release from FD-Dtx-NPs was acceptable for proposed usage. γ-irradiated NPs were sterile under all tested protocols and maintained their physicochemical properties at a 10-kGy cumulative dose, 0.500 Gy/s dose rate, and 5.57-h exposure. No significant differences were observed in physicochemical characteristics of FD-Dtx-NPs over 12 months. Finally, FD-Dtx-NPs showed a high anticancer activity in vitro. 
Conclusion: The proposed method generates FD-Dtx-NPs with reproducible characteristics, high activity, and elevated stability during the long-term storage. Results of γ-sterilization and stability studies may be valuable for the development of polymer-based drugs.