A pH-sensitive guar gum-grafted-lysine-beta-cyclodextrin drug carrier for the controlled release of 5-flourouracil into cancer cells

作者：Praphakar Rajendran Amarnath; Jeyaraj Murugan; Mehnath Sivaraj; Higuchi Akon; Ponnamma Deepalekshmi; Sadasivuni Kishor Kumar^*; Rajan Mariappan^*

来源：Journal of Materials Chemistry B, 2018, 6(10): 1519-1530.

DOI：10.1039/c7tb02551c

The physiological environment is a crucial factor in biomedical systems, which can be regulated with relative ease both in vitro and in vivo. Control of pH has emerged as a powerful strategy in cancer therapy because pH has a profound effect on the interaction of a polymeric-based drug delivery system with tumor cells. In this regard, the enhancement of pH response capability was demonstrated with a 5-flourouracil (5-FU)-loaded guar gum (GG)-grafted-lysine-beta-cyclodextrin (L-beta-CD) drug carrier. The size, charge, morphology, and encapsulation efficiency of the 5-FU-loaded polymeric carrier were characterized for the control and sustained release of the drug. In a specific cancer pH environment, 5-FU-loaded GG-g-L-beta-CD could rapidly swallow, disassemble, and release 5-FU by accepting or Losing electrons. In vitro observations indicate that GG-g-L-beta-CD dramatically releases 5-FU in an acidic environment rather than in a basic environment. In vitro antitumor activity tests showed that 5-FU-loaded GG-g-L-beta-CD had a higher cytotoxicity against KB cells, with an IC50 value of 1.38 mu g ml(-1). The reactive oxygen species (ROS) generated by 5-FU in the KB cells showed efficient suppression of tumour cell growth. The Hoechst assay revealed the active nature of 5-FU in the cell nucleus of the KB cells. The potential mitochondria) damage by apoptosis in KB cells greatly increased cell death. Therefore, due to its active nature, the pH-sensitive 5-FU-loaded GG-g-L-beta-CD carrier is a potential drug delivery system for safe and effective cancer therapy, and it can be useful for inhibiting tumour cell growth.

• 出版日期2018-3-14
• 单位中央民族大学