(M1530-02-10) Encapsulation of Cabazitaxel in Polymeric Nanoparticles and Its Biological Effect on Prostate Cancer Cells

Purpose: Prostate cancer is the second malignant disease more common in males and the second more frequent in Brazil. The main therapies for prostate cancer are hormonal control, surgery, radiotherapy, and chemotherapy. But, they show a high recurrence index and serious side effects. Thus, there is a search for new therapeutic strategies to enhance the lifetime of the patients and improve their well-being. An example of a new drug for prostate cancer therapy is cabazitaxel (CBZ). However, the application of this drug can lead to side effects, and its lipophilicity hinders its intravenous administration. Thus, the purpose of this work is the development and characterization of polymeric nanocapsule with cabazitaxel aiming to improve its intravenous administration and enhance its cytotoxic effect on prostate cancer cells.

Methods: The nanoparticles were prepared by the nanoprecipitation method and characterized by the mean size, polydispersity index (PDI), zeta potential by DLS, morphology by TEM, and crystallinity by DSC. In addition, the encapsulation efficiency (EE) and the release behavior of CBZ were evaluated. The activity of the nanoparticles was analyzed by in vitro cytotoxicity assay of free and encapsulated CBZ on prostate cancer cells (PC-3 and LNCaP). Also, there were performed hemolytic and opsonization assays to verify the compatibility of the nanoparticles with the human bloodstream.

Results: Polymeric nanocapsule optimized showed a spherical shape with a size around 200 nm, low polydispersity index, negative zeta potential, and high encapsulation efficiency (around 97%). The cabazitaxel encapsulated showed a continuous release profile for 100 hours. The IC50 of cabazitaxel encapsulated in nanocapsules was 5-fold lower than free cabazitaxel in prostate cancer cells PC-3. The hemolytic assay showed the compatibility of nanocapsule-cabazitaxel with the human bloodstream in concentrations of 5 to 25 µg/mL. The opsonization assay demonstrated that the complement system did not bind on the nanoparticles at higher concentrations.

Conclusion: The optimized nanocapsules improved the in vitro antitumoral effect of cabazitaxel and were compatible bloodstream indicating its potential for intravenous administration to treat prostate cancer.

References: Qu, N., Sun, Y., Xie, J. & Teng, L. Preparation and Evaluation of in vitro Self-assembling HSA Nanoparticles for Cabazitaxel. Anticancer. Agents Med. Chem. 17, 294–300 (2017).

Acknowledgements:This study was supported by the Sao Paulo Research Foundation (FAPESP) under Grant [#2018/ 13465-5]. This study is part of the National Institute of Science and Technology in Pharmaceutical Nanotechnology: a transdisciplinary approach INCT-NANOFARMA (FAPESP under Grant [#2014/50928-2]; and CNPq under Grant [# 465687/2014-8].