Advanced polymeric systems for colon drug delivery: from experimental models to market applications

In recent years, nano and micro drug delivery systems targeting the colon have gained more attention due to increasing interest in treating colon diseases such as colorectal cancer and inflammatory bowel disease, i.e., Crohn's disease and ulcerative colitis. Usually, nanocarriers are exploited for their enhanced permeability properties, allowing higher penetration effects and bioavailability, while microcarriers are primarily used for localized and sustained release. In bowel diseases, carriers must go into a delicate environment with a strict balance of gut bacteria (e.g., colon), and natural or biodegradable polymers capable of ensuring lower toxicity are preferred. However, these systems are primarily delivered orally, so the carrier must go through the whole gastrointestinal tract, where it encounters significant pH fluctuations, different mucus layers, several enzymes, and a long transit time. For this reason, various approaches have been explored and evaluated, especially using pH-responsive and time-dependent systems. This review provides an overview of the contemporary methodologies employed in orally administered nano- and microparticles for colon delivery, encompassing both in vivo and in vitro investigations. It evaluates their strengths, weaknesses, constraints, and potential enhancements, leveraging mathematical and microfluidic models. Furthermore, it focuses explicitly on systems that have already reached the market and are presently employed in treating severe colon diseases.