Design of resistant starch based composite nanoparticles as oral colon-specific drug vehicle for colon cancer treatment / Norulnazilah Ab’lah

Starch is constituted of amylose and amylopectin. Debranching of amylopectin converts it into amylose, thereby producing resistant starch which is known to be less digestible by the amylase. This study designed resistant starch using acid hydrolysis and heatmoisture treatment methods with native corn starch as the starting material. Heatmoisture treatment of native corn starch enabled the formation of resistant starch through amylopectin debranching and molecular weight reduction thereby enhancing hydrogen bonding between the starch molecules at the amorphous phase and gelatinization capacity. The nanoparticles prepared from resistant starch demonstrated similar drug release as those of native starch despite the resistant starch had a lower molecular weight. The resistant starch is envisaged to be resistant to the digestive action of amylase in the intestinal tract without the formed nanoparticles exhibiting excessively fast drug release in comparison to native starch. The resistant starch was subsequently used as the main excipient with chitosan as the co-excipient in designing composite nanoparticles as the oral-colon specific 5-fluorouracil carrier for colon cancer treatment. Chitosan-carboxymethyl 5-fluorouracil and chitosan-folate were conjugates and individually prepared via carbodiimide reaction. Resistant starch was introduced to strengthen the assembly of chitosan-carboxymethyl 5-fluorouracil conjugate and chitosan-folate conjugate into nanoparticles, allowing drug, targeting ligand and drug release modulator to co-exist in a single particle. Resistant starch composite nanoparticles were encapsulated into resistant starch/alginate beads and intra-capsular coated with pectin and ethylcellulose in situ. The bead encapsulation and intracapsular coating of resistant starch composite nanoparticles facilitated oral colonspecific drug delivery for local colon cancer treatment. Target delivery of nanoparticles at colon cancer site was envisaged to lead to cell uptake of nanoparticles with resistant starch composite nanoparticles exhibiting a relatively high level of cytotoxicity through inhibiting cell growth via cell cycle arrest at the G1 phase and negating cancer metastasis and drug efflux. The resistant starch composite nanoparticles were endocytosed by HCT 116 colon cancer cells via macropinocytosis. They are a potential carrier for cancer therapeutic delivery in local colon cancer treatment.