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 ± 59 nm for NPNS and 393 ± 66 nm for NPNSCS and zeta potentials of -15 ± 3 mV for NPNS to 10 ± 4 mV 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(-5)cm/s) was compared with NPNS (NPNS = 6.4-8.1 × 10(-6)cm/s and NPNSCS = 5.5-7.0 × 10(-6)cm/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 = 89 μM).
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