Chitin is the second-largest natural polymer after cellulose, and it exists widely in nature, such as shells of crustaceans such as shrimps, crabs, insects, and cell walls of fungi. Although chitin has good biocompatibility and biodegradability, its poor solubility limits its practicality in the field of biomedicine.
The product of chitin deacetylation is chitosan. Chitosan is structurally composed of D-glucosamine units, and each repeating glycoside unit has an amino group (-NH2) and two hydroxyl groups (-OH). The -NH2 group in the chitosan structural unit will be protonated to form -NH3+ ions in an acidic environment, and the free active amino group (-NH2) in the chitosan structure provides the easy modification of chitosan, often used to modify other groups. Studies have shown that when the degree of deacetylation of chitosan is greater than 50%, a large number of free amino groups (-NH2) on the chitosan structure make it easily soluble in acidic solutions. Chitosan has the same advantages as chitin in biocompatibility and biodegradability, and has unique biological properties, such as bioadhesion, high safety, antibacterial activity and antitumor activity.
By comparing the toxicity of chitosan oligosaccharides with different molecular weights and different degrees of deacetylation to prostate cancer cells PC3, lung cancer cells A549 and liver cancer cells HepG2, the researchers found that chitosan with low molecular weight and low degree of deacetylation has better antitumor effect. In addition, the scientists also evaluated the effect of deacetylation and pH on the antibacterial behavior of biomolecules, and found that the antibacterial efficiency was highest when the deacetylation and pH were lower. Through further exploration of its antibacterial mechanism, it was found that chitosan exerts antibacterial activity through two mechanisms: one is to interfere with bacterial metabolism by electrostatic accumulation on the surface of bacteria, and the other is to embed chitosan on deoxyribonucleic acid chains.
This process blocks the transcription of ribonucleic acid. The above research results show that chitosan has good antitumor and antibacterial properties, which are rarely possessed by other natural polymer materials. Chitosan also has a unique feature in structure, that is, the presence of primary amines at the C-2 position of the glucosamine residue, and the presence of primary amines provides chitosan with important biological properties.
Chitosan was originally commonly used in wound dressings, tissue engineering, etc. Due to the hydrophilicity and acid solubility of chitosan, it was difficult to be used as a drug carrier alone in clinical practice. Therefore, chitosan is often combined with citric acid and tripolyphosphate salts etc. are cross-linked to form complexes to increase their stability. At the same time, due to the cationic properties of its surface, it can also form polyelectrolyte complexes with polyelectrolytes with anions on the surface.
Nano-Drug Carrier of Chitosan
Nano-drug carriers generally refer to drug carriers whose particle size is in the nanometer size (1-100 nm) or composed of nano-sized materials. Because they exhibit many physical and chemical properties that traditional drug carriers do not have, it is a solution to traditional drug carriers in water solubility, targeting ability, biological toxicity and other issues, one of the most promising technologies, has attracted great attention of researchers in the field of medicine. In order to solve the problems of traditional drugs, many nano-drug carriers with different shapes and structures have been developed, such as nanoparticles, nano-tubes/rods, nano-hydrogels, nano-micelles and nano-vesicles, etc. There are core-shell structure, cavity structure, network structure and so on.
Thanks to the rapid development of nano-drug carriers, combined with the good biological properties of chitosan, chitosan-based drug carriers have increasingly become one of the hotspots in the field of drug delivery research. At the same time, in order to improve its bioavailability, different smart responsive drug carriers have been developed. For example, researchers have synthesized dual pH-responsive nanomicelles based on chitosan-vanillinimine, and the micelles are loaded with genistein. The nanomicelles are stable at physiological pH (about 7.4), while at pH outside cancer cells (about 6.8), the amino group in the carbonyl sulfide is protonated and positively charged, driving the micelles close to and Adsorbs to negatively charged cancer cells and subsequently enters cancer cells.
At low pH (about 5.0) in cancer cells, the pH-sensitive imine benzoate is cleaved, and the genistein-loaded nanomicelles are destroyed to release genistein for the purpose of cancer treatment, and reduce unnecessary loss of drugs during transport. In addition, there are temperature-sensitive drug carriers, light-sensitive drug carriers, glucose-sensitive drug carriers, and the like. Other researchers introduced controllable thermosensitive groups into carboxymethyl chitosan molecules to construct photothermally sensitive carboxymethyl chitosan nanosphere carriers, and loaded indocyanine green and doxorubicin at the same time. The optimal drug loading of indocyanine green and doxorubicin reached 23.46% and 21.27%, respectively. Combined with the good photothermal conversion effect of indocyanine green and the high chemotherapy efficiency of doxorubicin, a photothermal chemotherapy-based combination therapy drug system was established. It can generate reactive oxygen species and release doxorubicin under near-infrared radiation to realize photothermal chemotherapy, which can effectively inhibit the growth of HepG-2 cells. A photosensitive drug carrier was constructed by covalently combining the prodrug of 5-fluorouracil with low molecular weight chitosan through a photocleavable linker containing o-nitrobenzyl derivative, which was irradiated with 365 nm ultraviolet light. It decomposes to form o-nitrosobenzaldehyde and releases 5-fluorouracil.
During the process, unnecessary cytotoxicity is not caused due to the premature leakage and sudden release of the drug, and the biological safety performance of the drug is improved. In addition, some scientists have prepared a new type of glucose-sensitive chitosan-polyethylene oxide (chitosan/polyethylene oxide = 1: 0.5-1: 2.5) hydrogel, which can be Environmental glucose stimulation automatically regulates the release of metronidazole, and more drugs can be released at higher glucose concentrations, providing a new idea for the prevention or treatment of diabetic periodontitis. In addition to the above-mentioned intelligent nano-drug carriers based on chitosan, there are many studies on the preparation of new carriers by changing the carrier structure and ratio, and good results have also been obtained.