Sujittra Puntawee1,2, Man Theerasilp1,2, Somrudee Reabroi3, Rungnapha Saeeng4, Pawinee Piyachaturawat3, Arthit Chairoungdua3, Norased Nasongkla1,2. 1. a Department of Biomedical Engineering, Faculty of Engineering , Mahidol University , Nakorn Pathom , Thailand . 2. b Department of Chemistry and Center of Excellence for Innovation in Chemistry . 3. c Department of Physiology, Faculty of Science , Mahidol University , Bangkok , Thailand , and. 4. d Department of Chemistry, Faculty of Science , Burapha University , Chonburi , Thailand.
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.
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.
Authors: Daniel Cabrera; Alexander Wree; Davide Povero; Nancy Solís; Alejandra Hernandez; Margarita Pizarro; Han Moshage; Javiera Torres; Ariel E Feldstein; Claudio Cabello-Verrugio; Enrique Brandan; Francisco Barrera; Juan Pablo Arab; Marco Arrese Journal: Sci Rep Date: 2017-06-14 Impact factor: 4.379