Smart chitosan based microbead formulation for colon targeted delivery of lactoferrin

Abstract

Colorectal cancer, a global contributor to mortality, demands innovative therapeutic strategies to improve patient outcomes. There is a growing focus on targeted therapies and the development of new sustainable formulations that can effectively treat colorectal cancer while minimising the side effects of current chemotherapeutic treatments. Recent studies have shown that some forms of lactoferrin have the potential to treat various diseases and conditions, including infections, cancer, and inflammation. However, its therapeutic efficacy is limited by its rapid degradation in a highly acidic gastric environment. Therefore, the development of a controlled delivery system for lactoferrin could enhance its bioavailability and improve its therapeutic outcomes.  This study addresses the development of a novel multiresponsive formulation for the controlled delivery of lactoferrin.  First, gold-coated superparamagnetic iron oxide nanoparticles (Au-SPIONs) and dual responsive polyethylene glycol methacrylate-grafted-chitosan (PEGMA-g-Cs) copolymers were prepared. Next, gold-coated magnetic nanoparticles were loaded into the dual responsive PEGMA-g-Cs microspheres. Synthesised copolymers, nanoparticles, microspheres, and drug formulation were characterised via transmission electron microscopy (TEM), scanning electron microscopy (SEM), HNMR, X-ray diffraction, infrared spectroscopy, UV-visible spectrophotometer, optical microscopy, and dynamic light scattering. The drug loading and release studies of lactoferrin-loaded microbead formulations show excellent encapsulation efficiency, loading capacity, and release profile.  The drug release profiles in the gastrointestinal (GI) tract demonstrated minimal Lf release in acidic pH conditions and sustained release at a colonic pH. The findings of the MTT cell cytotoxicity assay in human CaCo-2 colon cancer cells show the reduction of cell proliferation after treatment with new formulations. These findings suggest that the new formulation could be a promising approach to improving the efficacy of colorectal cancer treatment. The ability to specifically target cancer cells while minimising damage to healthy tissues is a crucial advancement in the field of cancer treatment.