Existing studies have shown that chondroitin sulfate is a glycosaminoglycan that is widely present in connective tissues such as cartilage, bone, skin and blood vessels. In clinical practice, it is often used to treat joint-related diseases. Chondroitin Sulfate Thiol is a derivative produced by introducing a thiol group into chondroitin sulfate. This introduction can give it new chemical properties and expand its application in drug delivery systems. Adding thiol groups to the chondroitin sulfate structure can provide its original chemical reactivity, especially disulfide bond formation, which is very important for systems with targeted and sustained drug delivery requirements. In addition to chemical reactivity, thiolated chondroitin sulfate has the ability to form stable conjugates with more therapeutic agents, which enhances the pharmacokinetics and bioavailability of these drugs. This modification also allows the construction of controlled-release drug delivery systems that respond to the body's redox environment, especially in cancerous tissues with altered redox potential. The thiol groups on CST can form reversible disulfide bonds, which can be strategically cleaved in the presence of reducing agents like glutathione, abundant in tumor cells. This redox stimulus-responsive release profile enables targeted release of drugs at specific sites, such as cancerous tissues, thereby reducing systemic toxicity and improving therapeutic efficacy. This targeted delivery is crucial in cancer treatment, where high doses of chemotherapeutic agents often cause severe side effects.
Figure 1. Preparation, properties, functions and applications of chondroitin sulfate. (Shen Q, et al.; 2023)
Studies have found that CST has stronger mucoadhesive properties than unmodified chondroitin sulfate, making it particularly suitable for transmucosal administration (e.g., nasal, ocular, and oral). The thiol groups improve the interaction of CS with mucin in mucus, and this property prolongs the residence time of the drug loaded by CS at the absorption site. This increase in adhesion not only facilitates the sustained release of drugs, but also improves the permeability of drugs across the mucosal barrier. This feature is extremely helpful for drugs that require longer exposure for optimal absorption, ensuring more beneficial and consistent therapeutic effects. CST's mucoadhesive properties can help reduce the frequency of drug administration, enhancing patient compliance. Furthermore, the versatility of CSTs in forming a variety of drug delivery matrices, including hydrogels, nanoparticles, and micelles, highlights their potential for improving the delivery of a variety of therapeutic agents. Research shows that hydrogels made of CST can provide a protective environment for loaded drug molecules, enhance their stability and prolong their release. This is particularly useful for delivering proteins and peptides, which are prone to degradation. CST can form both nanoparticles that encapsulate hydrophilic drugs and micelles that can load hydrophobic drugs, and these systems protect them from degradation and allow controlled release. This encapsulation can also enhance the solubility of poorly soluble drugs, improving their bioavailability. In cancer therapy, CST-based nanodrug carrier particles can be designed with high permeability and retention (EPR) effect, which allows for better accumulation of cancer therapeutic drugs in tumor tissues. Once inside the tumor, the reducing environment can trigger the release of the encapsulated drug, ensuring the drug acts directly on the cancer cells while sparing healthy tissues. This targeted approach improves the efficacy of the drug while also reducing adverse side effects. In addition, CST also shows good application prospects in gene therapy. It can stably deliver nucleic acid molecules into cells. Because the thiol group of CST can cross-link CS with polycations to form a stable complex, thereby protecting nucleic acids from degradation by nucleases. These complexes can facilitate cellular uptake of nucleic acids and subsequent intracellular release, thereby achieving efficient gene transfer.
In conclusion, the drug delivery system composed of chondroitin sulfate thiol is a promising development direction of drug delivery technology. It can form stable, redox-sensitive drug conjugates, enhance targeting and controlled release of therapeutic agents, improve therapeutic efficacy and reduce systemic toxicity. CST has superior mucoadhesive properties compared to CS, which facilitates sustained and enhanced absorption of drugs across the mucosal barrier, making it suitable for more administration routes. Furthermore, the versatility of CST in forming hydrogels, nanoparticles, and micelles opens up new possibilities for delivering a wide range of drugs, from small molecules to large biomolecules. The biodegradability and biocompatibility of CST further ensure its safety for prolonged use, making it a valuable tool in developing advanced drug delivery systems. As research in this area progresses, CST-based delivery systems are poised to play a significant role in medicine, offering new solutions for treating various diseases and improving patient outcomes.
Alternate Names:
Chondroitin sulfate thiol
Chondroitin sulfate with a thiol group
Chondroitin sulfate sulfhydryl derivative
Chondroitin sulfate-SH conjugate
References:
1. Shen Q, et al.; A Review of Chondroitin Sulfate's Preparation, Properties, Functions, and Applications. Molecules. 2023, 28(20):7093.
2. Mallick N, et al.; Chondroitin sulfate-capped super-paramagnetic iron oxide nanoparticles as potential carriers of doxorubicin hydrochloride. Carbohydr Polym. 2016, 151:546-556.
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