Novel organic/inorganic hybrid nanoparticles as enzyme-triggered drug delivery systems: Dextran and Dextran aldehyde coated silica aerogels

Tiryaki E., Elalmis Y. B., Ikizler B. K., YÜCEL S.

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, cilt.56, 2020 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 56
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.jddst.2020.101517
  • Dergi Adı: JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, EMBASE
  • Anahtar Kelimeler: Colorectal cancer, Dextran, Silica aerogels, 5 fluorouracil, COLON-CANCER, THERMAL-ANALYSIS, ADSORPTION, 5-FLUOROURACIL, DEGRADATION, GLUTARALDEHYDE, OPTIMIZATION, MECHANISM, TRANSPORT, CELLULOSE
  • Yıldız Teknik Üniversitesi Adresli: Evet

Özet

Today, different therapeutic approaches are being developed because of the increased risk of colorectal cancer. In this context, we synthesized organic/inorganic hybrid nanoparticles using dextran (Dex) and dextran aldehyde (Dex-CHO) as organic polymers for the coating of inorganic silica aerogels. These Dex and Dex-CHO coated silica aerogels served as enzyme-triggered and colon targeted 5-Fluorouracil (5-FU) delivery systems. To improve the efficiency of drug loading and Dex/Dex-CHO coating, the surface of the silica aerogel was functionalized with 3-(aminopropyl)triethoxysilane (APTES). Enzyme-responsive drug release studies were performed with dextranase enzyme in simulated colonic fluid and cytotoxicity of aerogels on the colorectal adenocarcinoma cell line (Caco-2) were investigated by MTT assay. It was demonstrated that the release of 5-FU from Dex and Dex-CHO coated silica aerogels in simulated gastric and intestinal fluids was 1.7% and 3.4%, respectively, while the amount of 5-FU released from uncoated silica aerogels in these media was 86.4%. On the other hand, in the dextranase containing colonic medium 5-FU release in 12 h, straight after degradation of dextran by dextranase, was 24% and 13.4% from Dex and Dex-CHO coated silica aerogels, respectively. MTT assay results of unmodified, amine-modified, Dex and Dex-CHO coated silica aerogels did not show any significant cytotoxic effect on Caco-2 cells. However, MTT assay results of 5-FU loaded silica aerogels (unmodified, amine-modified, Dex and Dex-CHO coated) showed a decrease in the viability of Caco-2 cells. These results demonstrate that Dex and Dex-CHO coated silica aerogels are biocompatible nanoparticles that are not affected by the upper gastrointestinal regions and are powerful enzyme-triggered drug delivery systems for drug targeting to the colon area.