Colon Targeted Controlled Delivery of 5‐Fluorouracil Using Phosphazene‐Based Microspheres Encapsulated in Sodium Alginate

ABSTRACT In this study, a novel polyphosphazene–alginate composite microbead system was developed for the oral, colon‐targeted delivery of 5‐fluorouracil. Cross‐linked polyphosphazene microspheres (PHZ@MXDA) were synthesized via a precipitation reaction using hexachlorocyclotrifosphazene and m‐xylylenediamine. 5‐Fluorouracil was loaded onto the synthesized microspheres. Subsequently, the 5‐fluorouracil‐loaded microparticles were encapsulated in an alginate matrix containing quercetin to obtain 5‐FU/PHZ@MXDA/QUE‐MBs. The developed drug delivery system was characterized using FTIR, TEM, DLS, zeta potential, SEM‐EDS, XRD, and TGA analyses. Swelling and in vitro release studies in simulated GI environments revealed that the system exhibited significantly pH‐sensitive behavior, showing limited release in gastric conditions and higher drug release in the intestinal and colonic environments. The release kinetics confirmed a controlled‐release profile, with the highest goodness‐of‐fit observed for the zero‐order kinetic model under intestinal and colonic conditions. In antibacterial activity studies, 5‐FU/PHZ@MXDA/QUE‐MBs demonstrated an average zone of inhibition of 50 mm against Bacillus subtilis , Escherichia coli , and Enterococcus faecalis . MTT analyses performed on HT‐29 cells revealed that the formulation reduced cell viability in a dose‐ and time‐dependent manner and exhibited a higher cytotoxic effect than free 5‐fluorouracil after 72 h. Furthermore, the cell migration assay revealed a marked reduction in the migratory capacity of HT‐29 cells after treatment.