**19. Antitumor activity**

In some medical applications of chitin/chitosan, as antitumor compounds, for example, their degradation products are preferred, as they have a lower viscosity and a better solubility in water. The antitumor activity of chitin/chitosan is manifested by the stimulation of the immune system (production of lymphokines, including interleukins 1 and 2, stimulation of NK, etc.) [139-141]. Jeon and Kim in 2002, tested the antitumor activity of three kinds of COSs (high molecular weight ranging from 6.5 to 12 kDa – HMWCOS, medium molecular weight ranging from 1.5 to 5.5 kDa -MMWCOS, and low molecular weight ranging from 0.5 to 1.4 kDa – LMWCOS) against Sarcoma 180 solid (S180) and Uterine cervix carcinoma No. 14 (U14) [140]. The efficiency of tumor growth inhibition for both types of tumor cells in mice was best in the case of MMWCOS. There are many reports of S180 tumor cells being used for testing the antitumor activity of chitosan [141-142].

Maeda and Kimura 2004, investigated the antitumour effect of three water-soluble low molecular weight chitosans (21 kDa, 46 kDa, 130 kDa) and various doses of 650 kDa chitosan in sarcoma 180-bearing mice. They found that LMWC (21 and 46 kDa) and also smaller oligosaccharides could activate the intestinal immune system of animals, thus preventing tumor growth. But no antitumor effect was observed after the oral administration of chitosan samples, even of low molecular weight (46 kDa). The same authors confirmed that high molecular weight chitosan (650 kDa) prevents the adverse reactions of some cancer chemotherapeutic drugs [141]. Qin et al. in 2002 also tested the antitumor activity of LMWC against sarcoma 180, but they came to the opposite conclusions [143]. They noted that oral administration of LMW chitosan decreases the weight of the tumour [139, 142], although administration by intraperitoneal injection led to a higher inhibitory rate [142]. It was reported the higher the MW of LMWC, the better the tumor inhibitory effect [139]. The introduction of acidic groups as a result of chitosan oxidation has the opposite effect, and an increase in MW decreases antitumor activity. Qin Cai-qin et al in 2002, prepared low molecular weight chitosans by oxidative degradation with H2O2. They found that carboxyllc contents increased with decrease in molecular weight (M~). They also found that the introduction of carboxylic group is advantage to water-solubility of chitosan, but more acidic groups decrease the function of amino groups of chitosan against sarcoma 180 tumor. There is a correlation between the activity and the molecular weights of the oxidized chitosans, and a maximum of inhibition was found around 4 100 [143]. The influence of LMWC and COS (including the pentamer, hexamer, and higher oligomers) on the growth inhibition of Ehrlich ascites tumor (EAT) cells and tumor induced neovascularization was investigated [144]. Based on experimental results concerning the inhibition of angiogenesis and the induction of apoptosis, it was confirmed that COSs seem to be more potent angio inhibitory and antitumor compounds. Wang et al. reported that chitin oligosaccharides (DP 1-6) also reduced the number of K562 cells (human erythromyeloblastoid leukemia cell line) [145].

## **20. Chitosan applications**

#### **20.1. Biomedical**

18 The Complex World of Polysaccharides

**18. Analgesic activity** 

[136-137].

analgesic effect [138].

**19. Antitumor activity** 

**Figure 6.** Staphylococcus bacteria (a), covered with chitosan (b)

Some investigators reported that chitin and chitosan induce analgesia. Allan in 1984 found that chitosan provide a cool and pleasant soothing effect when applied to open wounds. Ohshima et al in 1987, reported that chitin proved excellent pain relief in 83 out of 91 cases who received the agent topically over open wounds such as burns, skin abrasion, skin ulcers, skin graft areas and so on [134-135]. Minami in 1993 and Okamoto in 1993, reported that animals did not feel pain when their wounds were covered with chitin and chitosan

Chitin and chitosan have been found to reduce the inflammatory pain due to intraperitoneal administration of acetic acid in rats [138]. When the chitosan suspension was mixed with acetic acid, the amino groups in C2 the position were protonated to NH3 subsequently the particles resolved in the solution. Bradykinin is one of the main substances related to pain and the levels of this substance decrease in the presence of chitin and chitosan. Chitin absorbs Bradykinin more extensively than chitosan and this could be one of the main

In some medical applications of chitin/chitosan, as antitumor compounds, for example, their degradation products are preferred, as they have a lower viscosity and a better solubility in water. The antitumor activity of chitin/chitosan is manifested by the stimulation of the immune system (production of lymphokines, including interleukins 1 and 2, stimulation of NK, etc.) [139-141]. Jeon and Kim in 2002, tested the antitumor activity of three kinds of COSs (high molecular weight ranging from 6.5 to 12 kDa – HMWCOS, medium molecular weight ranging from 1.5 to 5.5 kDa -MMWCOS, and low molecular weight ranging from 0.5 to 1.4 kDa – LMWCOS) against Sarcoma 180 solid (S180) and Uterine cervix carcinoma No. Potential applications of chitosan can only be exploited if its usable forms are properly developed and prepared. In solution and gel, it can be used as a bacteriostatic, fungistatic and coating agent. Gels and suspensions may play the role of carriers for slow release or controlled action of drugs, as an immobilising medium and an encapsulation material. Film and membranes are used in dialysis, contact lenses, dressings and the encapsulation of mammal cells, including cell cultures. Chitosan sponges are used in dressings, and to stop bleeding in mucous membranes. Chitosan fibres are used as resorbable sutures, non-wovens for dressings, and as drug carriers in the form of hollow fibres.

**Figure 7.** These are some ways you can shape the chitosan: films, gels, microspheres, tubes, sponges, powder
