In the present study, we have prepared nanosuspensions of piroxicam using Soluplus® as the matrix using aqueous-based conventional ball milling. The comparative physico-chemical characteristics were assessed using PXRD (powder X-ray diffraction), DSC (differential scanning calorimetry), FESEM (field emission scanning electron microscopy) and FTIR (Fourier transform infrared spectroscopy) analysis, indicating the nanoformulations displayed lower crystallinity with no chemical interactions between the drug and polymer molecules. The cytotoxicity of the formulations was established from MTT assay performed on Caco-2 cell lines. The release rate of piroxicam from various ratios of drug/polymer nanoparticles was investigated using a USP paddle apparatus. The nanoformulations exhibited higher release of the drug in comparison with the pure drug. The enhanced dissolution characteristics of the drug in the nanoformulations could possibly increase the anti-inflammatory effects of the drug owing to superior bioavailability characteristics.