18. Oral colon cancer targeting by chitosan nanocomposites

particulate mucoadhesion compared to blank

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• Grafted chitosan
• Carboxymethyl chitosan

particulate mucoadhesion compared to blank
		chitosan nanoparticles. It infers that such drug
		delivery system can confer a higher drug
		bioavailability
Gemcitabine	Gemcitabine loaded nanoparticles were prepared	The cytotoxicity of the gemcitabine loaded	[21]
	by ionic gelation method using chitosan and	nanoparticles in HT-29 colon cancer cell line
	Pluronic F-127 and their anticancer activity	is found to be satisfactory
	was tested in vitro by cell culture study
Hydroxycamptothecin	The chemotherapeutic drug hydroxycamptothecin	The nanoparticles adopted a sustained release	[22]
	was loaded into poly(lactide-co-glycolide)-	phase preceded by initial burst release of drug
	chitosan nanoparticles and its anticancer	that is reduced by chitosan coating. The
	activity was tested in vitro by cell culture study	cytotoxicity of the chitosan-based nanoparticles
		in A549 and HT29 cells is positive

(Continued)
Table 18.2 (Continued)

Candidate	Experiment	Remark	Reference
5-Fluorouracil	The chitosan-based formulation was converted	The chitosan-based formulation is susceptible to	[23]
	into tablet by compression coating technique	degradation by colonic enzymes which
	using granulated system	implies its possibility for use in oral colon-
		specific drug delivery
Survivin	The survivin was incorporated in mucoadhesive	The survivin-chitosan nanoparticles protect	[24]
	chitosan nanoparticles with the latter subjected	primary cells from autophagy and
	to molecular biology evaluation	successfully induce tumor-specific apoptosis
		via both extrinsic and intrinsic apoptotic
		pathways
Paclitaxel	Delivery system constituted of chitosan and	The highest mucin-producing cell line Calu-3	[25]
	glycerylmonooleate in 0.33M citric acid	cells are characterized by the lowest
	containing paclitaxel was designed and subjected	percentage of drug transport from gels in
	to drug transport study using different mucin-	comparison to Caco-2 cells
	producing cell lines (Calu-3, Caco-2)
Celecoxib	Films made of chitosan and guar gum were	Local high concentrations of drug are shown to	[26]
	prepared with celecoxib loading and subjected	impede the proliferation of HT-29 colon
	to anticancer activity evaluation	carcinoma cell directly, while chemo-
		prevention has been demonstrated using low
		drug doses in in vitro cell culture study
Iron loaded bovine	Fe-bLf or Taxol was adsorbed onto calcium	Fe-bLf or Taxol, as oral nanoformulations,	[27]
lactoferrin (Fe-bLf)	phosphate nanocores, enclosed in	provides a significant regression in the tumor
or paclitaxel	biodegradable chitosan and alginate	size as compared to intra-tumoral injection of
(Taxol)		Taxol
5-Aminolevulinic	Chitosan was mixed with sodium	The nanoparticles could exclude the influence	[28]
acid	tripolyphosphate and 5-aminolevulinic acid to	of normal flora inside the gut and serve as a
	form crosslinked nanoparticles	tool for fluorescent endoscopic detection of
		colorectal cancer cells in vivo

Oral colon cancer targeting by chitosan nanocomposites 415

4. Grafted chitosan

   1. Trimethyl chitosan

—
Trimethylated chitosan is a partially quarternized chitosan derivative that is freely soluble in water over a wide range of pH. It is obtained by reductive methylation of chitosan using methyl iodide in the presence of a strong base such as sodium hydrox- ide at 60^◦C [29 32]. This soluble chitosan derivative has mucoadhesive properties and exhibits good absorption-enhancing properties, even at neutral pH [33,34]. Its capability as absorption enhancer is ascribed to its ability to open the tight junctions between adjacent epithelial cells through interactions between the protonated (posi- tively charged) amino groups on the C-2 position and the negatively charged sites on the cell membrane and/or in the tight junctions [35]. Trimethyl chitosan has positive charges, independently of the pH, at all degrees of quarternization [36]. An increase in the degree of quarternization increases its permeation-enhancing effect [32,36,37]. Table 18.3 summarizes the outcome of trimethyl chitosan as nanocarrier of anticancer therapeutics for colon cancer treatment.

5. Carboxymethyl chitosan

Carboxymethyl chitosan is synthesized by introducing a carboxymethyl group in the parent structure of chitosan. It is prepared by carboxymethylation of the hydroxyl and amine moieties of chitosan. This modification increases chitosan’s solubility in neutral and basic solutions without affecting other important character- istics. Carboxymethyl chitosan nanoparticles have been prepared as carriers for some anticancer drugs. Carboxymethyl chitosan with different molecular weights

Table 18.3 Experimental studies of trimethyl chitosan as anticolon cancer drug nanocarrier

Candidate	Experiment	Remark	Reference
hSET1 antisense RNA and SN38 anticancer drugs	hSET1 antisense RNA and SN38 anticancer drugs were embedded in nanoparticles made of cysteine trimethyl chitosan and carboxymethyl dextran. The anticancer efficacy of nanoparticles was examined in vitro using HT29 cancerous cell line	The nanoparticles are found to exhibit anticancer activity via inhibiting topoisomerase that participates in the overwinding or underwinding of DNA	[38]

416 Applications of Nanocomposite Materials in Drug Delivery

and degrees of carboxymethyl substitution is used to prepare nanoparticles through ionotropic gelation with calcium ions [39]. Table 18.4 summarizes the outcome of carboxymethyl chitosan as nanocarrier of anticancer therapeutics for colon cancer treatment.

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