Effect of Semi-synthetic Andrographolide Analogue-loaded Polymeric Micelles on HN22 Cell Migration

  • Teeratas KANSOM Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand
  • Rungnapha SAEENG Department of Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand
  • Tanasait NGAWHIRUNPAT Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand
  • Theerasak ROJANARATA Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand
  • Prasopchai TONGLAIROUM Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand
  • Praneet OPANASOPIT Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand
  • Purin CHAROENSUKSAI Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand
Keywords: Andrographolide analogue, polymeric micelles, cell migration, oral cancer


Semi-synthetic andrographolide (AG) analogue, namely 19-tert-butyldiphenylsilyl-8,17-epoxy andrographolide, or 3A.1, is an anticancer drug. However, the major problem of 3A.1 is poor water solubility hindering its clinical applications. To improve the water solubility and anticancer potency of this analogue, 3A.1-loaded polymeric micelles employing N-naphthyl-N-O-succinyl chitosan (NSCS) as amphiphilic copolymer were prepared by the dropping method. The morphology, particle size, entrapment efficiency (%EE), and loading capacity (%LC) were evaluated. The 3A.1-loaded NSCS micelles were successfully prepared. These micelles were nano-size (66.26 to 102.53 nm) and with a spherical shape, with negative surface charge (-30.50 to -22.23 mV). The 3A.1-loaded NSCS micelles with 40 % drug loading exhibited the maximum values of both %EE (90.84 %) and %LC (25.95 %), indicating that a high amount of 3A.1 could be entrapped into the NSCS micelles. In addition, in vitro anticancer activity and cell migration assay on HN22 cells were evaluated. The 3A.1-loaded NSCS micelles exhibited stronger anticancer effect and cell migration suppression than the free drug. Therefore, these NSCS micelles containing 3A.1 may be potential nanocarriers for the treatment of oral cancer.


Download data is not yet available.


J Noguti, CFD Moura, GPD Jesus, VHD Silva, TA Hossaka, CT Oshima and DA Ribeiro. Metastasis from oral cancer: An overview. Cancer. Genom. Proteom. 2012; 9, 329-36.

D Sano and JN Myers. Metastasis of squamous cell carcinoma of the oral tongue. Cancer Metastasis. Rev. 2007; 26, 645-62.

S Irani. Distant metastasis from oral cancer: A review and molecular biologic aspects. J. Int. Soc. Prev. Commun. Dent. 2016; 6, 265-71.

MS Hossain, Z Urbi, A Sule and KM Rahman. Andrographis paniculata (Burm. f.) Wall. ex Nees: A review of ethnobotany, phytochemistry, and pharmacology. Sci. World. J. 2014; 2014, 274905.

U Sirion, S Kasemsook, K Suksen, P Piyachaturawat, A Suksamrarn and R Saeeng. New substituted C-19-andrographolide analogues with potent cytotoxic activities. Biorg. Med. Chem. Lett. 2012; 22, 49-52.

J Nateewattana, R Saeeng, S Kasemsook, K Suksen, S Dutta, S Jariyawat, A Chairoungdua, A Suksamrarn and P Piyachaturawat. Inhibition of topoisomerase II alpha activity and induction of apoptosis in mammalian cells by semi-synthetic andrographolide analogues. Invest. New Drugs 2013; 31, 320-32.

P Kumari, G Glosh and S Biswas. Nanocarriers for can-targeted drug delivery. J. Drug Target 2016; 24, 179-91.

W Sajomsang, P Gonil, S Saesoo, U Raktanonchai, W Srinuanchai and S Puttipipatkhachorn. Synthesis and anticervical cancer activity of novel pH responsive micelles for oral curcumin delivery. Int. J. Pharm. 2014; 477, 261-72.

C Liang, AY Park and JL Guan. In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro. Nat. Protoc. 2007; 2, 329-33.

A Grada, M Otero-Vinas, F Prieto-Castrillo, Z Obagi and V Falanga. Research techniques made simple: analysis of collective cell migration using the wound healing assay. J. Invest. Dermatol. 2016; 137, e11-e16.

T Woraphatphadung, W Sajomsang, P Gonil P, A Treetong, P Akkaramongkolporn, T Ngawhirunpat and P Opanasopit. pH-Responsive polymeric micelles based on amphiphilic chitosan derivatives: Effect of hydrophobic cores on oral meloxicam delivery. Int. J. Pharm. 2016; 497, 150-60.

MT Islam, ES Ali ES, SJ Uddin, MA Islam, S Shaw, IN Khan, SSS Saravi, S Ahmad, S Rehman, VK Gupta, MA Găman, AM Găman, S Yele, AK Das, JMCE Sousa, SMMM Dantas, HML Rolim, AAC Melo-Cavalcante, MS Mubarak, NS Yarla, JA Shilpi, SK Mishra, AG Atanasov and MA Kamal. Andrographolide, a diterpene lactone from Andrographis paniculata and its therapeutic promises in cancer. Cancer Lett. 2018; 420, 129-45.

Z Zhai, X Qu, H Li, Z Ouyang, W Yan, G Liu, X Liu, Q Fan, T Tang, K Dai and A Qin. Inhibition of MDA-MB-231 breast cancer cell migration and invasion activity by andrographolide via suppression of nuclear factor-κB-dependent matrix metalloproteinase-9 expression. Mol. Med. Rep. 2015; 11, 1139-45.

YC Lee, HH Lin, CH Hsu, CJ Wang, TA Chiang and JH Chen. Inhibitory effects of andrographolide on migration and invasion in human non-small cell lung cancer A549 cells via down-regulation of PI3K/Akt signaling pathway. Mol. Cell. Pharmacol. 2010; 632, 23-32.

HP Chao, CD Kuo, JH Chiu and SL Fu. Andrographolide exhibits anti-invasive activity against colon cancer cells via inhibition of MMP2 activity. Planta. Med. 2010; 76, 1827-33.

MJ Hsieh, JC Chen, We Yang, SY Chien, MK Chen, YS Lo, YT Hsi, YC Chuang, CC Lin, and SF Yang. Dehydroandrographolide inhibits oral cancer cell migration and invasion through NF-κB-, AP-1-, and SP-1-modulated matrix metalloproteinase-2 inhibition. Biochem. Pharmacol. 2017; 130, 10-20.

WT Zhu, SY Liu, L WU, HL Xu, J Wang, GX Ni and QB Zeng. Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer. Int. J. Nanomed. 2017; 12, 2621-34.

How to Cite
KANSOM, T., SAEENG, R., NGAWHIRUNPAT, T., ROJANARATA, T., TONGLAIROUM, P., OPANASOPIT, P., & CHAROENSUKSAI, P. (2018). Effect of Semi-synthetic Andrographolide Analogue-loaded Polymeric Micelles on HN22 Cell Migration. Walailak Journal of Science and Technology (WJST), 17(2), 88-95. Retrieved from http://wjst.wu.ac.th/index.php/wjst/article/view/5515