Background: Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable and biocompatible polymer which is widely used as a matrix to incorporate therapeutic agents. The anticancer activity of targeted folate-modified docetaxel-loaded PLGA nanoparticles (F-NP-Doc) was studied in vitro. Methods: Nanoparticles were prepared by a single-emulsion solvent-evaporation technique and characterized by physico-chemical methods. Cell survival was measured by the MTT assay and the sulforhodamine B assay. Folate receptor α expression, particle uptake and apoptosis were assessed by flow cytometry. Results: Folate-modified docetaxel-loaded PLGA nanoparticles showed high anticancer activity in vitro against HeLa cervical carcinoma cells and MCF7 breast adenocarcinoma cells overexpressing folate receptors. Targeted F-NP-Doc nanoparticles were more active compared to free docetaxel and non-targeted NP-Doc nanoparticles; in contrast, the activity of targeted nanoparticles against human fibroblasts (negative control) was significantly lower. F-NP-Doc particles, like free docetaxel, induced apoptosis in cancer cells. F-NP-Doc, but not unmodified docetaxel-loaded PLGA nanoparticles, reversed multidrug resistance of MCF7 R breast adenocarcinoma cells. High antitumor activity of F-NP-Doc has also been proven in in vivo experiments. Conclusions: The summarized experimental data brought us to the conclusion that the incorporation of docetaxel into the targeted PLGA nanoparticles dramatically improves its selectivity against cancer cells.

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Introduction. Docetaxel is widely used for cancer treatment. Actual issue for newly developed polymer-based Docetaxel formulations is applicability of current quality requirements. The technology of polymeric forms, including gamma-sterilization, are differ from actual Docetaxel injections technology. In this study were used PLGA-based particles with Docetaxel. The main attention was directed to studying qualitative and quantitative content of related impurities in polymeric forms during long-term storage and gamma-sterilization in comparison with pharmacopoeial requirements for Docetaxel injections.Aim. Studying of possible patterns of Docetaxel-related impurities formation between intact and gamma-irradiated batches.Materials and methods. Objects of study – lyophilizates of Docetaxel polymeric forms was previously obtained by the authors. Qualitative and quantitative analysis was performed by high pressure liquid chromatography.Results and discussion. Docetaxel-related impurities was determined and evaluated in the intact and gamma-treated batches. It was cleared, that related substances in the gamma-treated batches was different in comparison with non-treated but after vary storage periods.Conclusion. Docetaxel-loaded polymeric drugs shown proper stability during long term storage. The influence of gamma-treatment to Docetaxelrelated impurities content was found. Gamma sterilization can be promising method for novel drugs, but it needs individual study in the each case.