Formulation Development and in vitro Characterization of Regorafenib-loaded Polymeric Nanoparticles

Colorectal cancer (CRC), particularly in its recurrent metastatic form, continues to be a significant therapeutic challenge, with a 5-year survival rate of only 14% for advanced-stage patients. The incidence of advanced CRC has been rising by 3% annually among individuals younger than 50 years since 2010, underlining the need for novel treatment strategies. Regorafenib, a multi-kinase inhibitor, has shown efficacy in the treatment of recurrent metastatic CRC however its use is often limited by severe, sometimes fatal hepatotoxicity. To address these limitations, regorafenib was encapsulated in polymeric nanoparticles with the goal of reducing its non-specific biodistribution and associated side effects. An oil-in-water (O/W) emulsion solvent evaporation technique was used to develop regorafenib loaded mPEG-PLGA (methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles. The formulation was optimized for key parameters, including entrapment efficiency of regorafenib and particle size. Additionally, a robust analytical method was implemented for the quantitative detection of regorafenib using High Performance Liquid Chromatography (HPLC). Characterization of the nanoparticles was performed using Fourier-transform infrared spectroscopy (FTIR) to assess drug-polymer interactions, transmission electron microscopy (TEM) for morphological analysis, and in vitro drug release studies to evaluate the release kinetics of regorafenib from the nanoparticle formulation. The optimized regorafenib-loaded nanoparticles demonstrated a particle size of 238.1 nm, with a zeta potential of -8.2 mV and an entrapment efficiency of 68.2% ± 4.7%. FTIR analysis confirmed no drug-polymer interactions and encapsulation of drug while in vitro drug release studies revealed a sustained release profile for the encapsulated drug compared to regorafenib alone. All the results show that the regorafenib-loaded polymeric nanoparticles were successfully developed and may be beneficial in delivering regorafenib in a sustained manner to targeted site of action.