Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics.

Abstract:

: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.

journal_name

Biomacromolecules

journal_title

Biomacromolecules

authors

Zhang H,Mardyani S,Chan WC,Kumacheva E

doi

10.1021/bm050912z

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

1568-72

issue

5

eissn

1525-7797

issn

1526-4602

journal_volume

7

pub_type

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