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


OBJECTIVE
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.


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.


CONCLUSIONS
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.


CONCLUSIONS
Nanoencapsulation of AG 050-P implicated its potential development for clinical use in CCA treatment.
a Department of Biomedical Engineering, Faculty of Engineering , Mahidol University , Nakorn Pathom , Thailand .|b Department of Chemistry and Center of Excellence for Innovation in Chemistry .
Sujittra
S
Puntawee
a Department of Biomedical Engineering, Faculty of Engineering , Mahidol University , Nakorn Pathom , Thailand .|b Department of Chemistry and Center of Excellence for Innovation in Chemistry .
Man
M
Theerasilp
c Department of Physiology, Faculty of Science , Mahidol University , Bangkok , Thailand , and.
Somrudee
S
Reabroi
d Department of Chemistry, Faculty of Science , Burapha University , Chonburi , Thailand.
Rungnapha
R
Saeeng
c Department of Physiology, Faculty of Science , Mahidol University , Bangkok , Thailand , and.
Pawinee
P
Piyachaturawat
c Department of Physiology, Faculty of Science , Mahidol University , Bangkok , Thailand , and.
Arthit
A
Chairoungdua
a Department of Biomedical Engineering, Faculty of Engineering , Mahidol University , Nakorn Pathom , Thailand .|b Department of Chemistry and Center of Excellence for Innovation in Chemistry .
Norased
N
Nasongkla
D035685:Andrographis / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001652:Bile Ducts / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000473:pathology; D004224:Diterpenes / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D007773:Lactates / Q000737:chemistry*; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D004337:Drug Carriers; D007773:Lactates; D008823:Micelles; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; C030419:andrographolide
Andrographolide; anticancer; biodegradable polymer; controlled release; l-lactide); micelles; poly(ethylene glycol)-b-poly(d; polymeric drug delivery system; poorly water-soluble drugs