The Effect of Molecular Weight of Fucoidan on Chitosan/Fucoidan Nanoparticles via Oral Delivery System against Colon Cancer / 褐藻多醣分子量對幾丁聚醣/褐藻多醣奈米粒經口服傳輸系統對抗腸癌之影響

碩士 / 國立臺灣海洋大學 / 食品科學系 / 105 / Fucoidan is a complex sulfated polysaccharide that is found in brown algae. Recently, the diverse biological activities of fucoidan have been studied intensively. In particular, the antitumor activity has recently attracted considerable attention. Fucoidan has also been shown to induce a substantial reduction in viable cell numbers and apoptosis of human colon cancer HT-29 cells. Fucoidan polymers can modulate cell growth in different manners depending on their molecular weight. However, in the stomach and small intestine may lead hydrophilic macromolecules of fucoidan cannot diffuse across the cells through the lipid-bilayer cell membranes. In this study, fucoidan was extracted from the Laminaria japonica, hydrolyzed by hydrogen peroxide and subsequently fractionated using an ultrafiltration system, which produced three fucoidan fractions with different molecular weights. To overcome the poor oral bioavailability, a pH sensitive Chitosan/Fucoidan nanoparticle (CS/F NP) was prepared to against colon cancer. The objectives of this study were to determine the physicochemical properties of these fucoidan fractions and to investigate the relationship between their molecular characteristics and promote in vitro anticancer activity with CS/F NPs. We successfully prepared three fucoidan fractions with 436 kDa, 23-128 kDa and 8 kDa, named HF, MF and LF, respectively. The results suggest that the nanoparticles composed of chitosan and fucoidan were successfully prepared based on their electrostatic interaction. The size of CS/F NPs was around 149-228 nm. The CS/F NPs reveals significant pH sensitive property and high loading efficiency as the weight ratio of chitosan to fucoidan was 3:1. According to control release studies, the encapsulated fucoidan was released from NPs under simulated intestinal pH environment (pH=7.4). In vitro studies suggested that LF inhibited the growth of HT-29 cell better with the IC50 was 245.53 μg/mL. After preparation for CS/LF NPs, the IC50 was 203.29 μg/mL. Indicating that the preparation of fucoidan nanoparticles will not affect its anticancer activity. The results of transepithelial electric resistance (TEER) of Caco-2 show that NPs effectively enhanced opening of cell tight junctions. Briefly, all the results mentioned above suggest that LF should be explored as a potential anticancer agent, and the CS/F NPs developed in this study are a promising carrier for oral delivery of fucoidan against colon cancer and improve its bioavailability.

Identiferoai:union.ndltd.org:TW/105NTOU5253071
Date January 2017
CreatorsShiu, Sin-Yun, 許馨勻
ContributorsHuang, Yi-Cheng, 黃意真
Source SetsNational Digital Library of Theses and Dissertations in Taiwan
Languagezh-TW
Detected LanguageEnglish
Type學位論文 ; thesis
Format73

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