Improvement of the digestion stability and the colorectal cancer cellular uptake of EGCG through microsphere encapsulation

EGCG is a polyphenol which has been well known for its potential to affect human health and disease such as obesity and matabolic syndrome. Recently, some researches suggest that EGCG can inhibit the proliferation of colorectal cancer cells and the expression of indoleamine 2, 3-dioxygenase(IDO) which is an immunosuppresive enzyme. Thus, EGCG can be considered as a potential agent for antitumor immunotherapy. However, ECGC would be rapidly oxidized and broken down into small compounds in intestinal tract. Thus, it is different to reach colon and be absorbed by colorectal cancer cells. To improve its digestion stability, we will encapsulate EGCG into liposome to prevent it from oxidation and hydrolysis catalyzed by enzymes. In addition, we plan to make our drug carriers selectively deliver EGCG to colon cancer cells. Because the surface charge of cancer cells will become more negative due to aberrant sialylation in the progress of cancerization, we can use cationic liposomes as drug carriers to increase its selectivity. There are some factors which will affect this selectivity such as the level of surface charge, the charge mobility and the membrane fluidity of drug carriers. So, we will go deep to investigate their effects on the selectivity of drug delivery. However liposomes cannot protect EGCG in intestinal tract because of lipases, we need to further encapsulate liposomes into pH responsive materials to avoid premature drug release. In our cellular drug uptake experiments, we find liposome can enhance drug delivery efficiency. Fluid phase liposomes have more drug deliver efficiency than gel phase and positive surface potential liposomes can deliver more drug than neutral & negative surface potential liposomes during the same period. But, if liposomes have high positive surface potential, gel phase liposome can deliver more drug than fluid phase liposome. We also evaluate the physicochemical characterizations of different liposomes and find fluid phase liposomes have better encapsulation efficiency and small average size. However, liposomes can not keep inside of EGCG in wet preservation but some of them can still keep their surface potential. In coating material dissolution experiments, we find that coating material need to have pH-responsive solubility and sustained release properties to help them to deliver drug to large intestine.