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


Atli I., ÖZAY Ö.

Journal of Polymer Science, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1002/pola.70345
  • Dergi Adı: Journal of Polymer Science
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: 5-fluorouracil, alginate microcapsules, colon-targeted delivery, colorectal cancer, polyphosphazene
  • Çanakkale Onsekiz Mart Üniversitesi Adresli: Evet

Özet

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.