Therapeutic effect of orally administered microencapsulated oxaliplatin for colorectal cancer

Abstract

Colorectal cancer is a significant source of morbidity and mortality in the United States and other Western countries. Oral delivery of therapeutics remains the most patient accepted form of medication. The development of an oral delivery formulation for local delivery of chemotherapeutics in the gastrointestinal tract can potentially alleviate the adverse side effects including systemic cytotoxicity, as well as focus therapy to the lesions. Here we develop an oral formulation of the chemotherapeutic drug oxaliplatin for the treatment of colorectal cancer. Oxaliplatin was encapsulated in pH sensitive, mucoadhesive chitosan-coated alginate microspheres. The microparticles were formulated to release the chemotherapeutics after passing through the acidic gastric environment thus targeting the intestinal tract. In vivo, these particles substantially reduced the tumor burden in an orthotopic mouse model of colorectal cancer, and reduced mortality.

Oxaliplatin‐loaded crosslinked polymeric network of chondroitin sulfate‐co‐poly(methacrylic acid) for colorectal cancer: Its toxicological evaluation

“…Microparticles were formulated to release the chemotherapeutics after they passed through the acidic gastric environment and target the intestinal tract. In an in vivo study, these particles substantially reduced the tumor burden in an orthotopic mouse model of colorectal cancer and reduced the mortality rate …”

Polymeric nanoparticles for colon cancer therapy: overview and perspectives

“…For example, Urbanska et al loaded oxaliplatin into lipid-like polymeric nanoparticles which were further encapsulated in mucoadhesive micro-sized alginate based particles. 141 The in vivo results demonstrated an increased survival and decreased tumor progression after 17 weeks of orally delivering the formulation to the animals in comparison with the control group in a CRC orthotopic mouse model. Moreover, such NPs also led to a lower serum concentration of proinflammatory cytokines, lactoferrin, and the C-reactive protein.…”

The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery

“…Oral formulations deliv-60 ering chemotherapeutics to the colon are promising to improve 61 treatment of colorectal cancer [3], driven by the principle that tar-62 geted delivery of drugs to their intended cellular targets offers 63 opportunities for increasing treatment efficacy while minimising 64 the administered dose and associated side effects. Novel drug 65 delivery systems based on nanotechnology, such as nanoparticles 66 (NPs) [4] and nanoparticle-in-microcapsule systems [5], have 67 recently been developed for achieving colon-specific delivery of 68 therapeutic agents. Studies have shown that drug-loaded NPs can 69 exhibit higher anti-cancer activity than the corresponding drug 70 alone by enhancing the solubility of poorly water soluble drugs 71 and increasing drug uptake by cancer cells [6,7].…”