Nimesulide-loaded nanoparticles for the potential coadjuvant treatment of prostate cancer

Nimesulide (NS)-loaded nanoparticles (NPNS) were prepared from polylactide-co-glycolide (PLGA) and eventually coated with chitosan (NPNSCS). Nanoparticles (NP) were spherical with sizes 379±59nm for NPNS and 393±66nm for NPNSCS and zeta potentials of −15±3mV for NPNS to 10±4mV for NPNSCS, suggesting an efficient coating. Drug encapsulation rate was high (88±5% and 83±7% of added drug) for NPNS and NPNSCS, respectively. After NP washing and re-suspension, 98±2% and 99±1% of the drug initially entrapped remained associated to NP. NS was dispersed in amorphous state within the polymeric matrix. Two-fold dilution of NP with pH 7.4 PBS provoked no drug release. However, 30–40% NS was released after a 1/10 dilution. NPNSCS and NPNS diluted 1/100 reduced the encapsulated drug to around 30% and 70%, respectively. In contrast, 100% NS was released from NP under sink conditions in less than 2h. The permeability of free-NS (1–1.5×10−5cm/s) was compared with NPNS (NPNS=6.4–8.1×10−6cm/s and NPNSCS=5.5–7.0×10−6cm/s) using the PAMPA assay. The cytotoxicity of free-NS and NS in NP on model prostate cancer cells PC-3 and DU-145 showed the highest cytotoxic effect with NPNSCS on PC-3 cells (IC50=89μM).