Background: Colorectal cancer claims the life of millions of people globally. Chemoprevention is among the upcoming approaches for the treatment of colorectal cancer. It involves the use of therapeutic agents which are essentially not cytotoxic drugs but, however, impedes the carcinogenesis. Meloxicam (MLX) is one such agent which has the potential to be employed in the chemopreventive therapy of colorectal cancer. The aim of this study was to formulate MLX into a formulation so as to exploit its potential to the fullest.
Method: Conventional (M-MM) and PEGylated mixed micelles (M-PMM) of MLX were prepared using hydrogenated soy phosphatidylcholine (HSPC) and 1, 2-Distearoyl-phosphatidylethanolamine-methyl-polyethyleneglycol conjugate- 2000 sodium salt (MPEG 2000 DSPE) by the film casting method. The mixed micelles were fabricated using Quality by Design (QbD) approach and were optimized for parameters such as particle size and entrapment efficiency. The optimized formulation was further characterized for parameters such as particle size, percent entrapment efficiency, zeta potential, long-term stability, morphology, in vitro release and in vitro cytotoxic activity.
Results: The optimized PEGylated mixed micelles had high percent entrapment efficiency of 73.6%±0.72% and mean particle size of 132 nm±67nm and had a sustained release profile releasing 62.7%±0.37% drug in 24h. The M-PMM mixed micellar formulations revealed uniform size in the Small Angle Neutron Scattering (SANS) analysis and were found to be ellipsoidal shaped vesicles by transmission electron microscopy (TEM) as well as SANS studies. The entrapment of the MLX in the formulations was confirmed by Differential Scanning Calorimetry (DSC), Fourier Transform Infrared spectroscopy (FT-IR) and Powder X-Ray diffraction (PXRD) studies. Long term stability study indicated that the formulation was stable for three months. The cytotoxicity assay carried out in HT-29 cell lines showed that the PEGylated mixed micellar formulations had higher cytotoxicity than the conventional mixed micelles after 48 hours of incubation.
Conclusion: MLX loaded PEGylated mixed micelles had superior in vitro release as well as in vitro cytotoxicity. Hence, PEGylated mixed micelles can be considered to be a promising system for the delivery of MLX.