Development and Optimization of ZnO Nanoparticle-Embedded Fe3+-Crosslinked pH-Sensitive Carboxymethyl Cellulose/Poly(Vinyl Alcohol) Nanocomposite Beads: in Vitro Release Properties of an Anti-Cancer Drug

Purpose

This study aims to design and evaluate a carboxymethyl cellulose (CMC)/poly(vinyl alcohol) (PVA) nanocomposite drug delivery system incorporating ZnO nanoparticles for the controlled, pH-responsive release of sunitinib malate (SM). The work focuses on reducing burst release, improving cumulative drug release in the gastrointestinal tract, and examining the effect of ZnO nanoparticle amount on swelling behavior, entrapment efficiency, and drug release kinetics.

Methods

Zinc oxide (ZnO) nanoparticles were synthesized via the precipitation method. Subsequently, CMC/PVA nanocomposite beads incorporating ZnO nanoparticles and SM were fabricated using a gelation method with Fe³⁺ ions. XRD, FTIR, SEM-EDX, DSC, and TGA analyses confirmed the successful incorporation of ZnO nanoparticles into the beads and provided structural, morphological, and thermal characterization of both the nanocomposite beads and ZnO. The entrapment efficiency of SM, bead yield, and drug release behavior were evaluated as functions of polymer ratio, SM loading percentage, FeCl₃ concentration, and ZnO content. In addition, cytotoxicity was evaluated using the MTT assay for SM, SM-loaded CMC/PVA-ZnO nanocomposite beads, empty CMC/PVA-ZnO beads, and empty CMC/PVA beads without ZnO.

Results

The average bead size ranged from 1443.1 ± 145.8 to 1717.2 ± 61.5 μm. The maximum entrapment efficiency (40.14%) was achieved in beads containing 5% ZnO, compared to 33.91% in beads without ZnO. Incorporation of ZnO nanoparticles into the polymer matrix enhanced drug release. At pH 1.2 and pH 7.4, beads containing 25% ZnO exhibited the higher SM release, reaching 67.63% and 85.64%, respectively, compared to beads with 5% and 15% ZnO. The release kinetics of the nanocomposite beads were analyzed using five different drug release models. Cytotoxicity testing of SM-loaded nanocomposite beads via MTT assay confirmed their biocompatibility. Among the prepared formulations, beads with a CMC/PVA ratio of 5/1, FeCl₃ concentration of 0.2 M, SM amount of 10%, and ZnO content of 5% (B₅) demonstrated the most favorable characteristics, including the highest entrapment efficiency, controlled drug release profile, and optimal bead size.

Conclusion

According to the results, the prepared pH-sensitive nanocomposite beads, incorporating of ZnO nanoparticles with excellent properties, can be a promising candidate drug carrier for further research to release SM, which is used as a chemotherapy drug to treat various cancers.

Graphical Abstract