18. Oral colon cancer targeting by chitosan nanocomposites


Other chitosan derivatives


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Other chitosan derivatives


In addition to native chitosan and chitosan derivatives mentioned earlier, many other chitosan derivatives and composite formulations have been employed for designing nanoparticulate delivery systems for cancer therapeutics used in colon cancer treatment. Table 18.10 summarizes the outcome of alternative chitosan deri- vatives and formulations as nanocarrier of anticancer therapeutics for colon cancer treatment.


    1. Mechanism of oral colon cancer targeting


Chitosan nanocomposites have been designed for colon cancer targeting to promote specific killing of cancer cells, increase drug efficacy, and minimize unnecessary threats to the normal cells. With reference to oral colon cancer treatment, the nano- particulate systems of chitosan nanocomposites should primarily exhibit minimal premature drug release and confine the majority of drug fractions at colon regions [67]. Further, these nanoparticulate systems ideally should preferably gather at the tumor sites by passive or/and active targeting approaches.


    1. Passive targeting


Passive targeting is accompanied by accumulation of substrates at the target site due to enhanced permeability and retention effects as a result of leaky vasculature and incomplete lymphatic system surrounding cancers of soft tissue and epithelial cell origin [68]. The enhanced permeability and retention effect is associated with selec- tive accumulation of macromolecular drugs in tumor tissues. Such effect is derived from fast tumor growth and angiogenesis mediated by vascular endothelial growth factors and other growth factors to meet the nutrition and oxygen demands of tumors [69,70]. The newly formed tumor vessels have abnormal form and architecture. They are constituted of poorly aligned endothelial cells with wide fenestrations where the endothelial pore size varies from 10 to 1000 nm [71]. For efficient extravasation from the fenestrations of the endothelial tissue, a substrate should have sizes below 400 nm. Practically, this has been possible with drugs delivered using polymer-drug conjugate systems, polymeric nanoparticles, micelles, or liposomes [72].



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