Enhanced oral bioavailability and biodistribution of atractylodin encapsulated in PLGA nanoparticle in cholangiocarcinoma.

Autor: Omar AI; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Bangkok, Thailand., Plengsuriyakarn T; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Bangkok, Thailand., Chittasupho C; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand., Na-Bangchang K; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Bangkok, Thailand.; Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University (Rangsit Campus), Bangkok, Thailand.
Jazyk: angličtina
Zdroj: Clinical and experimental pharmacology & physiology [Clin Exp Pharmacol Physiol] 2021 Mar; Vol. 48 (3), pp. 318-328. Date of Electronic Publication: 2020 Dec 15.
DOI: 10.1111/1440-1681.13433
Abstrakt: Atractylodes lancea (Thunb) DC. and its bioactive compound atractylodin (ATD), have been shown to exert promising anticancer activity against cholangiocarcinoma (CCA) both in vitro and in vivo. However, the clinical development of ATD could be hindered due to hydrophobicity and poor pharmacokinetic properties, and thus, the requirement of high dose administration and the risk of toxicity. In the present study, ATD-loaded in PLGA nanoparticles (ATD-PLGA) and that coated with chitosan (ATD-PLGA-CS) were developed using nanoprecipitation and single emulsification methods, respectively. The optimized ATD-PLGA formulation provided superior physical and pharmaceutical properties over ATD-PLGA-CS. The antiproliferative activity of ATD-PLGA against the two CCA cell lines, HuCCT1 and CL6, and the normal cell line (OUMS-36T-1F) was evaluated using MTT assay. Results showed that normal epithelial cell was less sensitive to ATD-PLGA compared to both CCA cell lines. In mice, the radiolabelled 99m Tc-ATD-PLGA showed superior pharmacokinetic profile over free 99m Tc-ATD, as evidenced by a 2.7-fold increase of area under plasma concentration-time curve (AUC 0-∞ ), maximum plasma concentration (C max ), time to C max (t max ), and mean residence time (MRT). Higher accumulation of 99m Tc-ATD-PLGA was observed in vital organs/tissues such as blood, liver, heart, and kidney, compared with free 99m Tc-ATD-PLGA. Altogether, the results suggest that PLGA NPs could be a suitable drug delivery carrier for ATD in CCA.
(© 2020 John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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