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

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 mic...

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Bibliographic Details
Published in:Biomacromolecules 2006-05, Vol.7 (5), p.1568-1572
Main Authors: Zhang, Hong, Mardyani, Sawitri, Chan, Warren C. W, Kumacheva, Eugenia
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - toxicity
Applied sciences
Biocompatible Materials - chemical synthesis
Biological and medical sciences
Biological Transport
Cell Survival - drug effects
Chitosan
Exact sciences and technology
Gels
General pharmacology
HeLa Cells
Humans
Hydrogen-Ion Concentration
Medical sciences
Methotrexate - pharmacokinetics
Methotrexate - toxicity
Microchemistry
Molecular Conformation
Natural polymers
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Physicochemistry of polymers
Starch and polysaccharides
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Summary: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.
ISSN:1525-7797
1526-4602
DOI:10.1021/bm050912z