18. Oral colon cancer targeting by chitosan nanocomposites

Chitosan as anticancer drug for colon cancer treatment

Previous research and review articles report that chitin (N-acetyl-D-glucosamine oligomers) and chitosan (D-glucosamine oligosaccharide, COS) have anticancer properties. Chitosan can inhibit tumor cells directly by interfering cell metabolism, inhibiting cell growth, and inducing cell apoptosis. It also exhibits anticancer activ- ity through enhancing the body’s immune function. Several studies suggest that chitosan has antitumor effects in vitro and in vivo:

1. 
   Chitosan exhibits its chemo-preventive influence against colon cancer by increasing quinone reductase (QR) and glutathione S-transferases (GST) activities, and glutathione (GSH) con- centration by impeding ornithine decarboxylase (ODC) activity and cyclooxygenase-2 (COX-2) expression in vitro [8].
   
2. 
   COS reduces pro-inflammatory cytokine-mediated nitric oxide (NO) synthesis, iNOS (inducible NO synthase) expression, and invasiveness of HT-29 cancer cell lines [9,10].
   
3. 
   COS demonstrates antiangiogenic activity through inhibiting heparanase enzymatic activ- ity [11].
   
4. 
   Chitosan and chitin induce lymphocyte cytokines through increased T-cell proliferation. Their antitumor activity is enhanced by acquired immunity through T-cell differentiation [12].
   
5. 
   Low molecular weight chitosan is found to be more effective in cancer suppression than high molecular weight counterpart [13].
   

Table 18.1 summarizes the outcomes of experimental studies where chitosan is deemed to exhibit anticancer property.

3. Chitosan as drug carrier for colon cancer treatment

   1. Native chitosan

Native chitosan has received widespread applications in designing nanoparticu- late drug delivery systems for cancer therapeutics. With reference to colonic tumor targeting, it can interact with anionic drugs to form complexes, protect the drugs from premature release at the upper gastrointestinal tract and has the drugs released specifically at the colon region via chitosan degradation through glycosidic linkage lysis by means of enzymatic actions of the colonic micro- flora [16].
Table 18.2 summarizes the outcome of experimental studies of native chito- san as a nanovehicle of anticancer therapeutics with respect to colon cancer treatment.
Table 18.1 Experimental studies of chitosan as an anticancer drug

Candidate	Experiment	Remark	Reference
Chitosan Chitosan-kimchi Chitosan oligosaccharide Low and high molecular weight chitosan	The effects of chitosan oligosaccharide on pro- inflammatory cytokine-induced NO production and invasiveness of human colorectal adenocarcinoma HT-29 cells were investigated The anticancer effects of chitosan-added kimchi were investigated by using in vitro cellular system with HT-29 human colon carcinoma cells Two different kinds of chitosan namely 1. soluble chitosan—90% degree of deacetylation and 3 cps viscosity, and 2. nonsoluble chitosan—95% degree of deacetylation and 22 cps viscosity were used in the study Chitosan oligosaccharide was investigated for its role in colon cancer chemo-prevention in HT-29 cells The anticancer activity of chitosan was investigated in chemical-induced colonic pre- cancerous lesions inflicted ICR mice over a duration of 6 weeks	Chitosan inhibits cytokine-mediated NO production, iNOS expression, and invasiveness of HT-29 cells The soluble chitosan-added kimchi and nonsoluble chitosan-added kimchi are stronger growth inhibitors to HT-29 cells than the kimchi itself Chitosan oligosaccharide has colon cancer chemo- preventive activity. It increases QR and GST activities and GSH levels by inhibiting ODC activity and COX-2 expression in vitro Both low molecular weight chitosan and high molecular weight chitosan-fed mice are found to have lower levels of aberrant crypt foci than the untreated mice	[10] [14] [9] [15]

Table 18.2 Experimental studies of native chitosan as anticolon cancer drug nanocarrier

Candidate	Experiment	Remark	Reference
Chitosan-	The anticancer property of chitosan-pentasodium	The nanogels exhibit time-dependent	[17]
pentasodium	tripolyphosphate/alginate nanogels was	antiproliferative responses in human colon
tripolyphosphate/	investigated in vitro using human colon cancer	cancer cells
alginate nanogels	cells (HT29 and CaCo2)
Curcumin	The mucoadhesive and release characteristics of	The curcumin loaded nanoparticles exhibit	[18]
	curcumin contained in chitosan nanoparticles,	therapeutic benefits in the treatment of colon
	prepared through ionically gelled with	cancer through prolonged therapeutic
	tripolyphosphate anions, were investigated	retention and delivery
Silver nanoparticles	The cytotoxic efficacy of the silver nanoparticles	The silver nanoparticles loaded chitosan	[19]
	loaded in chitosan nanocarrier in human colon	nanocarrier demonstrates effective anticancer
	cancer HT 29 cells was examined	activity in mammalian cells through inducing
		cellular apoptosis at very low doses of silver
		nanoparticles
Curcumin	Curcumin loaded chitosan-based mucoadhesive	The ex vivo study shows that curcumin loaded	[20]
	nanoparticles were designed to deliver	chitosan nanoparticles demonstrate improved
	curcumin to the colon