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Published on: December 23, 2016
Tailorable thiolated trimethyl chitosans for covalently stabilized nanoparticles
Rolf J Verheul1, Steffen van der Wal, Wim E Hennink
1Departments of Pharmaceutics and Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3508 TB, The Netherlands.
Biomacromolecules
|June 29, 2010
Summary
A new four-step method synthesizes thiolated trimethylated chitosan (TMC) with tunable properties. These thiolated TMCs form stable nanoparticles and show reduced cytotoxicity, offering potential in drug delivery applications.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Drug Delivery
Background:
- Chitosan derivatives are widely explored for biomedical applications.
- Trimethylated chitosan (TMC) offers improved solubility and charge characteristics.
- Thiolation introduces disulfide bond formation, enhancing material stability and functionality.
Purpose of the Study:
- To develop a novel, controllable method for synthesizing partially thiolated trimethylated chitosan (TMC).
- To characterize the synthesized thiolated TMCs regarding degree of quaternization and thiolation.
- To evaluate the stability, cytotoxicity, and nanoparticle-forming capabilities of the novel thiolated TMCs.
Main Methods:
- A four-step synthesis involving N-carboxylation, dimethylation, quaternization, and cystamine conjugation.
- Characterization using (1)H NMR, Ellman's assay, and gel permeation chromatography.
- Assessment of pH-dependent stability, cytotoxicity (XTT and LDH assays), and nanoparticle formation with ovalbumin.
Main Results:
- Successfully synthesized thiolated TMCs with tailorable degrees of quaternization (25-54%) and thiolation (5-7%).
- Demonstrated pH-dependent disulfide cross-linking of thiolated TMCs at pH 7.4, with stability at pH 4.0.
- Thiolated TMCs exhibited reduced cytotoxicity compared to non-thiolated analogs and formed stable nanoparticles with hyaluronic acid.
Conclusions:
- A versatile method for producing functionalized thiolated TMCs was established.
- The thiolated TMCs offer enhanced stability through disulfide bond formation, particularly in nanoparticle formulations.
- These novel thiolated chitosan derivatives show promise for advanced drug delivery systems due to improved stability and biocompatibility.
