Abstract
Andrographolide analog, namely 19-tert-butyldiphenylsilyl-8,17-epoxy andrographolide (or 3A.1) has been reported to be a potential anticancer agent for several types of cancer. Due to its poor aqueous solubility, 3A.1 was incorporated within self-assembly polymeric nanoparticles made of naphthyl-grafted succinyl chitosan (NSC), octyl-grafted succinyl chitosan (OSC), and benzyl-grafted succinyl chitosan (BSC). These 3A.1-loaded nanoparticles were nanosized (< 200 nm) and spherical in shape with a negative surface charge. 3A.1-loaded nanoparticles were produced using a dropping method, which 40% initial drug adding exhibited the highest entrapment efficiency. The release of 3A.1 from the 3A.1-loaded nanoparticles displayed a delayed release pattern. Under acidic conditions (pH 1.2), there was no free drug release. After the pH was adjusted to 6.8, a high cumulative 3A.1 release was obtained which was dependent on the hydrophobic moieties. These 3A.1-loaded pH-sensitive nanoparticles proved to be beneficial for specifically delivering anticancer drugs to the targeted colon cancer sites. In vitro anticancer activity against HT-29 found that the 3A.1-loaded nanoparticles had significantly lower IC50 than that of the free drug and promoted apoptosis. Additionally, in vitro wound-healing migration on HN-22 revealed that free 3A.1 and the 3A.1-loaded nanoparticles inhibited cell motility compared with untreated cells. These pH-sensitive amphiphilic chitosan nanoparticles may be promising nanocarriers for oral anticancer drug delivery to colorectal cancer cells.
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The authors gratefully acknowledge the Commission of Higher Education (Thailand) and the Thailand Research Fund through the Golden Jubilee Ph.D. Program (Grant No.PHD/0077/2558), the International Research Network Fund (IRN58W0004), and National Natural Science Foundation of China (NSFC 81561148012) for their financial support.
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Kansom, T., Sajomsang, W., Saeeng, R. et al. Apoptosis Induction and Antimigratory Activity of Andrographolide Analog (3A.1)-Incorporated Self-Assembled Nanoparticles in Cancer Cells. AAPS PharmSciTech 19, 3123–3133 (2018). https://doi.org/10.1208/s12249-018-1139-4
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DOI: https://doi.org/10.1208/s12249-018-1139-4