Introduction

The present invention relates to biocompatible polymeric nanoparticles for the combined administration of two substances of natural origin endowed with antiproliferative activity for the treatment of a tumor type. These nanoparticles consist of a mixture of poly (ε-caprolactone) and poly (D, L-lactic-co-glycolic acid) -poly (ethylene glycol), and loaded with suitable quantities of Trans-Resveratrol (RSV) and Celastrol (CL). Specifically, the invention contemplates the preparation of said polymeric nanoparticles loaded with resveratrol and celastrol, and their use to convey said active substances in the treatment of prostate cancer.

Technical features

In all prostate cancer cell lines tested (C-42; DU-145; and PC-3 cells) the combination of unencapsulated RSV + CL produces an increase in cytotoxicity, compared to treatment with RSV or CL used alone, possibly due to an additive effect. The encapsulation of RSV or CL in NP determines an increase in cytotoxicity compared to the profiles observed for free molecules. NPs loaded with the combination of RSV + CL show significantly higher antiproliferative activity than both the non-encapsulated combination and even the single encapsulated molecules. The results show that the co-administration of RSV + CL encapsulated in the NPs of the present invention determines a significant and unexpected enhancement of the anticancer effects, compared to those of the single molecules (encapsulated or not) and of their non-encapsulated combination, attributable to an effect synergistic.

Possible Applications

• Controlled release of natural chemopreventative agents;
• Synergistic effect of combination with improvement of the effectiveness of single agent;
• Combination anticancer therapy.

Advantages

• Co-administration of bioactive agents;
• Increasing of solubility and chemical stability of the nano-encapsulated compound(s), reducing their potential systemic toxicity, controlling their release and improving the overall bioavailability;
• Significant improvement of anti-tumor efficacy.