Portal de Periódicos da CAPES

Design of Biocompatible Chitosan Microgels for Targeted pH-Mediated Intracellular Release of Cancer Therapeutics

2006; American Chemical Society; Volume: 7; Issue: 5 Linguagem: Inglês

10.1021/bm050912z

1526-4602

Hong Zhang, Sawitri Mardyani, Warren C. W. Chan, Eugenia Kumacheva,

Polymer Surface Interaction Studies

We report the rational design of a chitosan-based drug delivery system. The chitosan derivative N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) was ionically cross-linked by sodium tripolyphosphate (TPP) to form sub-200-nm microgels that are responsive to pH changes. When these microgels were loaded with methotrexate disodium (MTX), a cytotoxic drug for cancer treatment, and conjugated to the targeting biomolecule apo-transferrin, a protein known to enter cells via receptor-mediated endocytosis, enhanced killing of immortalized HeLa cells was observed. In this intracellular delivery method, the microgel was exposed to low-pH environments that caused the chitosan to swell and release the drug. This rational drug delivery design may be useful in enhancing cancer therapy and reducing side effects.