pH-responsive sodium alginate/CMCS/CMCNa composite hydrogel beads for sustained delivery of 5-fluorouracil-β-cyclodextrin inclusion complexes

Colorectal cancer chemotherapy often faces challenges such as rapid drug clearance, non-specific biodistribution, and burst release, leading to systemic toxicity and reduced therapeutic efficacy. To overcome these limitations, this study developed a colon-targeted sustained-release hydrogel bead system based on β-cyclodextrin (β-CD) and biocompatible polymers (CMCS/CMCNa/SA). The results demonstrated that the incorporation of β-CD significantly enhanced the drug loading capacity through host–guest interactions. Under the optimal mass ratio of drug complex to wall material (15 : 35), the encapsulation efficiency reached as high as 81.23%. Drug release kinetics showed high correlation coefficients (R2 > 0.9) in zero-order, first-order, Higuchi, and Korsmeyer–Peppas models, indicating a diffusion-controlled release mechanism. The β-CD-modified hydrogel matrix effectively sustained the release of 5-fluorouracil (5-Fu) within the therapeutic window while minimizing the initial burst release. In conclusion, this intelligent delivery system takes advantage of the host–guest inclusion of β-CD and the pH-responsive properties of the polymers, showing promise for localized treatment of colorectal cancer.