Investigation of cross-linking and conjugation effects in the use of TiO2-polymer nanocomposites as controlled drug release systems

TUNCER C., BÜTÜN ŞENGEL S., BÜTÜN V.

Chemical Papers, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1007/s11696-026-05061-4
  • Dergi Adı: Chemical Papers
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aerospace Database, Chemical Abstracts Core, Materials Science & Engineering Collection (ProQuest), Technology Collection (ProQuest)
  • Anahtar Kelimeler: Controlled drug release, Cross-linking effect, Drug conjugation, Grafted polymer, Higuchi model, Ibuprofen, Korsmeyer-Peppas, Release kinetics, TiO₂
  • Eskişehir Osmangazi Üniversitesi Adresli: Evet

Özet

TiO2-polymer nanocomposite structures in both linear and cross-linked forms were synthesized via protected monomer using the surface-initiated atom transfer radical polymerization (SI-ATRP) technique. The Ti-PMAA and Ti-PMAA-co-PEGDMA systems were synthesized by grafting uncross-linked PMAA and cross-linked PMAA-co-PEGDMA chains onto the surface of TiO2 nanoparticles using methacrylic acid (MAA) and/or ethylene glycol dimethacrylate (EGDMA) monomers. Additionally, a conjugated system (Ti-PMAA-C) was prepared by covalently attaching ibuprofen to the polymer backbone via ester linkage. The TiO2-polymer nanocomposites were evaluated as controlled drug delivery systems with ibuprofen. Drug loading studies revealed comparable loading capacities for the physically loaded systems (Ti-PMAA: DLC 6.17%, DLE 87.72%; Ti-PMAA-co-PEGDMA: DLC 6.23%, DLE 88.51%), with loading amounts of 65.79 and 66.38 mg/g, respectively. Comparative release studies revealed that both cross-linking and conjugation strategies significantly enhanced drug delivery capacity. The Ti-PMAA-co-PEGDMA achieved the highest cumulative release of 65.6 mg/g (1.75-fold improvement), while Ti-PMAA-C reached 64.0 mg/g (1.71-fold enhancement), compared to 37.5 mg/g for the Ti-PMAA system after 13 days. Despite nearly identical drug loading, release efficiencies differed markedly: 98.8% for Ti-PMAA-co-PEGDMA versus 57.0% for Ti-PMAA, demonstrating that enhanced release performance is governed by polymer architecture rather than loading capacity. Kinetic analysis demonstrated that the Higuchi model best described all three systems (R2 = 0.935–0.978), confirming diffusion-controlled release. Korsmeyer-Peppas analysis revealed distinct release mechanisms correlated with polymer architecture: classical Fickian diffusion for Ti-PMAA (n = 0.505), anomalous transport for Ti-PMAA-co-PEGDMA (n = 0.607) indicating swelling-assisted diffusion, and quasi-Fickian behavior for Ti-PMAA-C (n = 0.451) characteristic of hydrolysis-controlled release. These findings define structure–property relationships for designing TiO2-based polymer drug delivery systems.