18. Oral colon cancer targeting by chitosan nanocomposites

Active targeting

The success of an anticancer therapy is dependent on selective drug accumulation in tumor tissue, and ultimate target site of tumor namely cell membrane, cytosol, or nucleus [73]. This can be facilitated through specific recognition of drug substrate

Table 18.10 Experimental studies of alternative chitosan derivatives and formulations as anticolon can- cer drug nanocarrier

Candidate	Experiment	Remark	Reference
Gambogic acid 5β-Cholanic acid	L-arginine and chitosan were used to prepare N- octyl-N-arginine chitosan conjugate of which was then transformed into nanoparticles as drug carrier Glycol chitosan-5β-cholanic acid, a water-soluble, biocompatible, biodegradable and self- aggregating conjugate polymer was transformed into nanoparticles with Cy5.5 added as a near- infrared dye Paclitaxel nanoparticles were prepared through encapsulating in synthetic/bio macromolecular shell made of chitosan and dextran sulfate using a layer-by-layer self-assembly technique Surface modifications of these core-shell nanoparticles were performed by covalently conjugating with poly(ethylene glycol) H(2)N- PEG-carboxymethyl and fluorescence-labeled wheat germ agglutinin to build a biocompatible and targeted drug delivery system A thermally responsive nanogel was developed through radical polymerization of chitosan and N-isopropylacrylamide with acrylamide	The micelles formed from N-octyl-N-arginine chitosan conjugate provide excellent drug loading, drug solubilization and absorption enhancement effects for gambogic acid The nanoparticles exhibit good potentials to target therapeutic drugs to colon cancer CT26 cells and metastatic tumors	[58] [59]
Paclitaxel Coumarin		Thirty two % of paclitaxel are released from four bilayers of biomacromolecule assembled nanoparticles within 8 h of dissolution as compared with more than 85% of drug released from the bare nanoparticles High cell viability with polyethylene glycol conjugation and high binding capacity of fluorescence-labeled wheat germ agglutinin modified nanoparticles with Caco-2 cells are observed. The biocompatible and targeted nanoparticulate drug delivery system may be considered as a potential candidate for the treatment of colon cancer The nanogels adopt thermal therapy and chemotherapy approaches in disease treatment	[60] [61]

(Continued)
Table 18.10 (Continued)

Candidate	Experiment	Remark	Reference
Camptothecin	Pluronic F127 and chitosan-based camptothecin	The introduction of Pluronic F127 and chitosan to	[62]
	loaded poly(lactic-co-glycolic acid)	the nanoparticle surfaces significantly enhances
	nanoparticles were formulated	the therapeutic efficacy of drug in multidrug
		resistant colon tumor-bearing mice
Gold	The curcumin loaded chitosan-graft-poly(N-vinyl	The colon tumor localization studies reveal that the	[63]
nanoparticles	caprolactam) nanoparticles containing gold	nanoparticles are retained in tumor for a week
and curcumin	nanoparticles were developed by ionic
	crosslinking method
Bovine	Alginate-enclosed, chitosan-conjugated, calcium	The nanocarrier activates both extrinsic as well as	[64]
lactoferrin	phosphate, iron-saturated bovine lactoferrin	intrinsic apoptotic pathways to induce apoptosis
	nanocarriers/nanocapsules were developed	in cancer cells and cancer stem cells, without
		inducing any nonspecific nanotoxicity. It also
		inhibits angiogenesis thus negating cancer
		growth
siRNA	Imidazole-modified chitosan and trimethylchitosan/	The nanoparticles can be used as a potential	[65]
	siRNA nanoparticles were formulated for	therapeutic approach to treat CDX2-dependent
	targeting at CDX2	gastric lesions
Interleukin-12	Interleukin-12 was entrapped in plasmid DNA	Plasmid DNA loaded chitosan nanoparticles at N/	[66]
plasmid DNA	loaded chitosan nanoparticles. Their cytotoxicity	P 5 16 exhibit minimal cytotoxicity. They can be
loaded	and transfection efficiency in murine CT-26	used as a suitable candidate for interleukin-12
chitosan	colon carcinoma cells were examined	delivery as inferred from study using murine CT-
nanoparticles		26 colon carcinoma cells

Oral colon cancer targeting by chitosan nanocomposites 425

via its surface decorated ligand by diseased site that expresses biomarkers distin- guishing such site from the surrounding healthy tissues [68,70,71]. Active targeting requires the substrate to be decorated with ligands such as monoclonal antibody, leptin, transferrin, folic acid, or others. Nanoparticles have been recognized as a vehicle that can be passively accumulated in tumor tissue following enhanced per- meation and retention effects [74]. There can also be internalized with drug delivery being greatly improved by having a high affinity targeting ligand attached on the matrix and ligand with innate ability to activate receptor-mediated endocytosis [73]. Through receptor-mediated endocytosis processes, the tumor cells can be directly killed against normal cells.

15.