Solubility enhancement and in vitro evaluation of PEG-b-PLA micelles as nanocarrier of semi-synthetic andrographolide analogue for cholangiocarcinoma chemotherapy

Abstract

Background: Semi-synthetic andrographolide analogue (19-triphenylmethyl ether andrographolide, AG 050) is a C-19 substituted andrographolide which is the major constituent from Andrographis Paniculata Nees (Acanthaceae). The analogue has previously been reported to be highly cytotoxic against several cancer cell lines. Nevertheless, its poor water solubility limits clinical applications of this compound.

Objectives: To improve the aqueous solubility and bioavailability of AG 050 by protonation and encapsulation in poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-b-PLA) polymeric micelles.

Materials and methods: PEG-b-PLA micelle was employed as a nanocarrier for AG 050. The physicochemical properties and in vitro cytotoxicity against cholangiocarcinoma (CCA) (KKU-M213) cell line were done in this study.

Result and discussion: Hydrochloride salt of AG 050 (AG 050-P) greatly enhanced the solubility of this compound (15-fold). PEG-b-PLA was able to encapsulate AG 050-P in hydrophobic core with a significant increase in the amount of AG 050-P in aqueous solution (280-fold). Film sonication method provided greater results in drug-loading study as compared to micelles via solvent evaporation. In addition, the encapsulated AG 050-P exhibited sustained release pattern and excellent cytotoxicity activity against KKU-M213 with IC₅₀ of 3.33 µM.

Conclusion: Nanoencapsulation of AG 050-P implicated its potential development for clinical use in CCA treatment.

• Andrographolide
• anticancer
• biodegradable polymer
• controlled release
• micelles
• poly(ethylene glycol)-b-poly(d
• l-lactide)
• polymeric drug delivery system
• poorly water-soluble drugs

Acknowledgements

The authors thank Dr. Banchob Sripa from liver Fluke and Cholangiocarcinoma Research Center, and Department of Pathology, Faculty of Medicine, Khon Kean University for providing the KKU-M213 cell line.

Declaration of interest

This research project is supported by Mahidol University, Thailand. The financial support for Sujittra Puntawee from the Center of Excellence for Innovation in Chemistry (PERCH-CIC) is gratefully acknowledged.