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


Tiryaki E., Elalmış Y. , Karakuzu İkizler B., Yücel S.

Journal Of Drug Delivery Science And Technology, cilt.56, no.101517, ss.1-13, 2020 (SCI Expanded İndekslerine Giren Dergi)

  • Cilt numarası: 56
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.jddst.2020.101517
  • Dergi Adı: Journal Of Drug Delivery Science And Technology
  • Sayfa Sayıları: ss.1-13

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.