Carboxymethyl chitosan (CMCS) is a promising development in drug delivery, using its chemo mechanical and biocompatibility to enhance treatment effectiveness and patient outcomes. Chitosan is a naturally occurring polysaccharide from chitin that is widely known for its biodegradability, non-toxicity, and films, beads, and gel properties — it is a multifunctional biomedical material. But its insoluble nature in neutral and basic pH conditions has meant that it isn't widely available for some drug delivery. Chitosan carboxymethylated – introduces carboxymethyl groups into the backbone of chitosan and makes it more subitizable at a wider pH range without destroying its antimicrobial properties. This chemistry turns chitosan into carboxymethyl chitosan, a water-soluble polymer with huge promise in future drug delivery systems.
Figure 1. Carboxymethyl chitosan based targeted drug delivery and tissue engineering applications.(Upadhyaya L, et al.; 2014)
Probably the greatest strength of CMCS in drug delivery is that it is more soluble and stable in the body, and thus has more predictable and regular patterns of drug release. This carboxymethylation adds not only more solubility, but functional groups that can be incorporated into the carrier and bind to multiple therapeutic molecules making CMCS an even more versatile carrier. This increased solubility allows CMCS-based drug delivery systems (nanoparticles, hydrogels, micelles, etc.) to be created which could encapsulate and shield drugs from degradation on the way to their target. Also, CMCS with the carboxyl and amino groups provides multiple drug-binding sites, which makes it possible to form stable drug-carrier complexes, increasing the bioavailability and therapeutic index of the drugs in CMCS. Also, the chemical structure of CMCS gives it mucoadhesive features which are particularly useful for use in mucosal-tissue based drug delivery applications (oral, nasal, and ocular drug delivery). The fact that CMCS sticks to the mucosa increases the time the drug delivery system spends in the absorption zone, which improves drug absorption and bioavailability. This mucoadhesive effect results from the CMCS carboxymethyl groups interacting with mucin proteins found in the mucus layer to create a tight adhesive that can endure the varying environment of mucosal tissues. This property is especially useful when administering drugs that need a longer-term engagement with the mucosal surface to produce the best therapeutic effect (eg, vaccines, hormones, peptides). The biodegradability and biocompatibility of CMCS make it attractive for safe and effective drug delivery platforms. After a dose, CMCS-derived drug carriers can be catalyzed by the body's natural enzymes into non-toxic waste products that minimize adverse reactions and keep the carrier from accumulating in the body. This property is especially valuable for chronic and long-term medications, for which repeated doses of carrier drug could result in toxic complications if not fully degradation. What's more, CMCs' biocompatibility means that it will not trigger serious immune responses, and is suitable for a variety of biomedical uses, such as tissue engineering, wound healing and gene delivery. The CMCS has also been extensively studied as a host for small molecule therapeutic molecules, proteins and nucleic acids in recent years. CMCS-based nanoparticles, for example, have been invented to deliver anticancer drugs that have better targeting and fewer side effects than traditional chemotherapy. The CMCS's ability to form stable complexes with nucleic acids has also been applied to gene delivery where CMCS carriers can both guard the genetic code against degradation and enable it to be assimilated by the cell target. This versatility makes CMCS an ideal tool for the construction of next-generation drug delivery systems that overcome the drawbacks of current treatments and yield more benefit to patients. Also, with the potential to change the surface of CMCS carriers by chemically conjugating or coating them with ligands, targeted drug delivery systems can be created. Scientists can get specific delivery of drugs to a cell or tissue by grafting targeting moieties – antibodies, peptides, small molecules, etc. – onto the surface of CMCS-based carriers. This selective therapy does not only increase drug therapeutic potency but also reduces systemic toxicity by reducing off-target side effects. For instance, CMCS nanoparticles infused with folic acid selectively engage folate receptor-overexpressing cancer cells for more concentrated drug absorption into the tumor and increased anticancer activity.
CMCS is also very good at forming films, which is perfect for making drug-loaded films and patches for transdermal delivery. These movies offer the controlled dispensing of medication over a long period of time which helps to improve patient follow-up and convenience. The adaptability of CMCS in the form of films, nanoparticles, hydrogels and micelles that can be formulated make it useful for an array of therapeutic targets. it's this flexibility that makes CMCS an attractive candidate for the development of personalized medicine, in which drugs are delivered to the body at a specific rate that meets the individual patient's demands. As a component of advanced wound dressings, CMCS has been effective as an antimicrobial and tissue regeneration agent in wound healing. Hydrogels and films made of CMCS can dry the wound surface, shield it from infection, and introduce drugs like antibiotics and growth factors to the wound. These properties can be used to speed up the healing and boost the quality of the newly produced tissue. Because CMCS is capable of drug delivery and wound healing in combination, it is an ideal material to use for making multifunctional wound dressings to improve chronic and acute wound healing. In sum, carboxymethyl chitosan is a promising new delivery system that provides an open, biocompatible platform for creating new drug delivery systems. The improved solubility, stability, mucoadhesive and stable drug-carrier complex making it an ideal candidate for numerous therapeutic applications. With the current research, there is enormous potential for CMCS-based drug delivery systems to further enhance the effectiveness and safety of current therapies to improve patient outcomes and medicine.
Alternate Names:
CM-chitosan
Carboxymethylated chitosan
Chitosan carboxymethyl ester
Carboxymethylated chitosan derivative
Chitosan carboxymethylate
Chitosan-COOH
Carboxymethyl chitosan salt
References:
1. Upadhyaya L, et al.; The implications of recent advances in carboxymethyl chitosan based targeted drug delivery and tissue engineering applications. J Control Release. 2014, 186:54-87.
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