## 4 Conclusions  
The use of food-grade polymers in systems for targeted delivery of bioactive substances to the colon is gaining considerable interest in recent years. This approach is particularly useful for improving the bioavailability and efficacy of nutraceuticalids, which are known to have beneficial health effects but are often limited by poor absorption and rapid metabolism.  
Food polymers, which are nontoxic, biocompatible, and biodegradable, can serve as carriers for bioactive substances and protect them from degradation and premature release in the gastrointestinal tract. This approach may also improve their targeted delivery to the colon, where they can exert their health-promoting effects.  
The strategies basing the delivery of drugs in the ileo-colonic region on a single stimulus (i.e., transit time, pH or bacterial enzymes) can be dramatically affected by the large inter- and intra-individual variability that characterize the GIT physiology and, most importantly, its pathological conditions. For this reason, more recently, new formulations which try to subordinate the drug release to two or more physiological stimuli have been proposed [155]. Such a dual or combined (multi-faceted) approach may act sequentially or in parallel. Sequential trigger systems contain for instance two or more layers, each sensitive to different stimuli, e.g., pH and time, that can be activated one after the other and release the entrapped drug along the intestinal tract. Parallel systems instead combine different drug release mechanisms operating simultaneously. One possible advantage is that is one of the mechanisms do not work correctly for a strong physiological variability (e.g., too rapid transit time, abnormal low pH values, or severe disbiosis), the drug release can still be activated by the other mechanism(s).  
Multi-stimuli strategies have been mainly applied for the functional coating tablets, pellets and capsules also in colon targeted commercial drugs [156; 157; 158; 159]. However, the same principles could be promising also if used for nutraceuticalids. Therefore, the expectation from the research in this field is that even new and better-performing associations of food-grade polymers can enter the market, achieving increasingly effective control and efficacy of colon drug delivery.  
The technological characterization remains critical in the development of these systems. Morphology, size, surface charge, encapsulation efficiency, and release kinetics are key parameters that can influence their behavior and interaction with biological systems. For example, the size and surface charge of the carrier can affect cellular uptake and adhesion to intestinal epithelium.  
The evaluation of stability and biological activity is also of crucial importance in assessing the efficacy and safety of polymer-based carriers and their bioactive cargo. Stability studies can determine the shelf life of the system and its ability to maintain the bioactivity of the loaded substance. Biological activity studies can confirm the therapeutic effects of the delivered bioactive substance and validate the potential of the system in the treatment of gastro-intestinal disorders.  
In conclusion, using food-grade polymers to produce new formulations for color-targeted delivery of bioactive substances is a valid approach to improve the local bioavailability and efficacy of nutraceutical ingredients. Technological characterization and evaluation of stability and biological activity are critical to develop effective and safe products for the treatment of colonic disorders.  
Conceptualization, S.R. and R.P.; writing--original draft preparation, S.R., E.Z., A.R. and R.L.; writing--review and editing, S.R. and R.P.; supervision, R.P. All authors have read and agreed to the published version of the manuscript.  
This research received no external funding.  
Not applicable.  
The authors declare no conflict of interest.