Gelatin microsphere-alginate hydrogel combined system for sustained and gastric targeted delivery of 5-fluorouracil

AYCAN D., Gül İ., Yorulmaz V., ALEMDAR YAYLA N.

International Journal of Biological Macromolecules, cilt.255, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 255
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.ijbiomac.2023.128022
  • Dergi Adı: International Journal of Biological Macromolecules
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, INSPEC, Veterinary Science Database
  • Anahtar Kelimeler: Alginate, Gelatin, Microsphere-hydrogel system
  • Marmara Üniversitesi Adresli: Evet

Özet

In the current study, novel gelatin microspheres/methacrylated alginate hydrogel combined system (5-FU-GELms/Alg-MA) was developed for gastric targeted delivery of 5-fluorouracil as an anticancer agent. While water-in-oil emulsification method was used for the production of 5-FU-GELms, Alg-MA was synthesized through methacrylation reaction occurred by epoxide ring-opening mechanism. Then, 5-FU-GELms/Alg-MA hydrogel system was fabricated by the encapsulation of 5-FU-GELms into Alg-MA hydrogel network via UV-crosslinking. To evaluate applicability of fabricated 5-FU-GELms/Alg-MA as gastric targeted drug delivery vehicle, both swelling and in vitro drug release experiments were carried out at pH 1.2 medium resembling gastric fluid. Compared to drug release directly from 5-FU-GELms, 5-FU-GELms/Alg-MA hydrogel system showed more controlled and sustained drug release profile with lower amount of cumulative release starting from early stages, since hydrogel matrix created a barrier to the diffusion of 5-FU included in microspheres. Drug release kinetic results obtained by applying various kinetic models to release data showed that the mechanism of 5-FU release from 5-FU-GELms/Alg-MA hydrogel system is controlled by Fickian diffusion. All results revealed that 5-FU-GELms/Alg-MA hydrogel integrated system could be potentially utilized as gastric targeted drug carrier to enhance therapeutic efficacy and reduce systemic side effects in gastric cancer treatments for future studies.