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Preparation and Characterizations of RSPP050-Loaded Polymeric Micelles Using Poly(ethylene glycol)-b-Poly(ε-caprolactone) and Poly(ethylene glycol)-b-Poly(D,L-lactide).

RSPP050 (AG50) is one of the semi-synthetic andrographolide that is isolated from Andrographis paniculata NEES (Acanthaceae). The anti-proliferation effects of AG50 against cholangiocarcinoma (HuCCT1) were displayed high cytotoxicity. Unfortunately, poor water solubility of AG50 limited its clinical applications. This study aimed to increase the concentration of AG50 in water and drug loading and release study in phosphate-buffered saline (PBS) in the absence/presence of pig liver esterase enzyme. Cytotoxicity of AG50-loaded polymeric micelles was evaluated against HuCCT1. AG50 loaded micelles were prepared by film sonication and encapsulated by polymers including poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) or poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-b-PLA). Micelle properties were characterized such as solubility, drug loading, drug release and in vitro cytotoxicity against HuCTT1. AG50 was successfully loaded into both types of polymeric micelles. The best drug-polymer (D/P) ratio was 1 : 9. AG50/PCL and AG50/PLA-micelles had small particle size (36.4±5.1, 49.0±2.7 nm, respectively) and high yield (58.2±1.8, 58.8±2.9, respectively). AG50/PLA-micelles (IC50=2.42 µg/mL) showed higher cytotoxicity against HuCCT1 than AG50/PCL-micelles (IC50=4.40 µg/mL) due to the higher amount of AG50 released. Nanoencapsulation of AG50 could provide a promising development in clinical use for cholangiocarcinoma treatment.