Development of docetaxel-loaded folate-modified Poly(lactic-co-glycolic acid) particles

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.