Paclitaxel encapsulated in cationic liposomes: A new option for neovascular targeting for the treatment of prostate cancer

Abstract

Neovascular targeting is an established approach for the therapy of prostate cancer (PCa). Cationic liposomes have been shown to be absorbed by immature vascular endothelial cells due to negative electric charge of their outer cell membrane. We aimed to evaluate the antitumoural efficacy of paclitaxel encapsulated in cationic liposomes for the treatment of PCa. Tumours were generated by subcutaneous injection of 106 MatLu tumour cells into the right hind leg of 21 male Copenhagen rats. After tumour growth, the animals were treated by an i.v. infusion with either 5% glucose (Gl), paclitaxel (Pax), cationic liposomes (CL) or paclitaxel encapsulated in cationic liposomes (EndoTAG-1) on days 12, 14, 16 and 19. Treatment was initiated on day 12 after tumour inoculation at mean tumour volumes of 0.31±0.13 mm3. On the last day of treatment, animals treated with EndoTAG-1 had the significantly lowest tumour volumes with 2.49±0.84 cm3 vs. Pax (5.59±0.45 cm3) vs. CL (3.87±1.25 cm3) vs. GL (5.17±1.70 cm3). The quantification of MVD showed the lowest count for EndoTAG-1-treated tumours (11.78±2.68 vessels/mm2) followed by Gl (15.64±6.68 vessels/mm3), Pax (18.22± 9.50 vessels/mm3) and CL (40.9±32.8 vessels/mm3). The data confirm that neovascular targeting with EndoTAG-1 is a promising new method for the treatment of PCa by reducing the primary tumour mass and demonstrating benefits in the suppression of angiogenesis in comparison with the conventional treatment.