18. Oral colon cancer targeting by chitosan nanocomposites

N-succinyl chitosan

N-succinyl chitosan is a chitosan derivative obtained by the incorporation of succi- nyl moieties into the N-terminal group of the glucosamine units. Like other deriva- tives, N-succinyl chitosan exhibits good water solubility in a broad pH range, and it is also considered biocompatible both in vitro and in vivo. N-succinyl chitosan is initially developed as a wound dressing material combined with collagen. It is also recognized as an excellent cosmetic ingredient [36]. Table 18.5 summarizes the out- come of N-succinyl chitosan as nanocarrier of anticancer therapeutics for colon can- cer treatment.

7. PEGylated chitosan

Grafting of hydrophilic polymers such as polyethylene glycol (PEG) onto chitosan is a common strategy to enhance the solubility and biocompatibility of chitosan as well as to achieve lower recognition by the host immune system and improve blood circula- tion time [45]. These PEG chains generate a barrier layer to prevent the adhesion of opsonins existing in the blood, so that the particles can be “invisible” to phagocytic cells. Due to these advantages, chitosan-g-PEG copolymer has been prepared and uti- lized to develop various types of nanocarriers for colon cancer drug delivery. Chitosan-g-PEG nanoparticles have been prepared by ionotropic gelation with tripoly- phosphate as the crosslinker [46]. Table 18.6 summarizes the outcome of PEGylated chitosan as nanocarrier of anticancer therapeutics for colon cancer treatment.

8. Hyaluronic acid—coupled chitosan

Nanoparticles made of large molecular weight chitosan are deemed to have high matrix porosity than those of low molecular weight chitosan. The dependency of nanoparticle porosity on chitosan molecular weight has a profound effect on the adsorption of hyaluronic acid on the nanoparticles. The hyaluronic acid apparently is able to penetrate deeply into the more porous high molecular weight (684 kDa) chitosan nanoparticles, while it forms a corona around those composed of more densely crosslinked low molecular weight (25 kDa) chitosan. The differences in mode of hyaluronic acid deposition onto/into nanoparticles imply that the way of hyaluronic acid presenting to biomolecules will differ. This has specific relevance in relation to interactions of nanoparticles with hyaluronic acid receptors (e.g.,

Table 18.4 Experimental studies of carboxymethyl chitosan as anticolon cancer drug nanocarrier

Candidate	Experiment	Remark	Reference
Doxorubicin hydrochloride	Chitosan-based nanogels were prepared by electrostatic interaction between chitosan and carboxymethyl chitosan using tripolyphosphate and calcium chloride as the respective ionic crosslinker In vitro cellular uptake, mucoadhesion, and cytotoxicity profiles of nanoparticles were examined using colon cancer cell line (Caco-2) Curcumin and 5-fluorouracil were encapsulated in N,O-carboxymethyl chitosan nanoparticles, and have their anticancer activity examined in vitro in HT29 cell culture Polyelectrolyte complex composed of chitosan and O-carboxymethyl chitosan as a pH responsive carrier for oral delivery of doxorubicin hydrochloride was designed In vitro drug release, ex vivo intestinal adhesion, and permeation profiles of nanoparticles were examined	The nanogel exhibits prolonged contact with the intestinal mucosa and improves local drug concentration. The nanogel shows potential to be used as drug delivery vehicle for the treatment of colon cancer	[40]
Curcumin and 5-fluorouracil		Combination drugs formulated in the form of nanoparticles exhibit enhanced anticancer effects	[41]
Doxorubicin hydrochloride		Oral administration of nanoparticles is effective in delivering doxorubicin hydrochloride systemically, giving an absolute bioavailability of 42%	[42]

418 Applications of Nanocomposite Materials in Drug Delivery