ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1600525
Dihydroartemisinin-sodium taurocholate-PLGA nanoparticles: A novel therapeutic approach against cystic echinococcosis
Provisionally accepted- 1College of Veterinary Medicine, Xinjiang Agricultural University, Ürümqi, China
- 2Xinjiang Key Laboratory of New Drug Study and Creation for Herbivorous Animal, Urumqi, China
- 3Department of Abdominal Surgery, The Third People Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
- 4State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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Dihydroartemisinin (DHA) demonstrates potent anti-echinococcal activity. However, its clinical application is constrained by non-specific biodistribution and low bioavailability. To overcome these limitations and enhance hepatic targeting, the DHA was encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles, and using sodium taurocholate (STC) as the surface modifier, a novel composite nanoparticle designated as DHA-STC-PLGA nanoparticles (DSP nanoparticles). The formulation was optimized using response surface methodology, and its targeting efficiency was confirmed through in-vivo fluorescence imaging. Both in vitro and in vivo studies were conducted to evaluate the therapeutic efficacy and elucidate the underlying mechanisms of DSP nanoparticles in a murine model of cystic echinococcosis. The results showed that the optimal preparation conditions of DSP nanoparticles were 40mg/mL STC, a DHA/PLGA1:10, ultrasonic power (UP) of 80, and oil in water (O/W) ratio was 1:20. Under these conditions, the DSP nanoparticles size were 125.73 ± 1.78 nm, exhibited a sustained release of DHA, and maintained stability for up to 42 days. DSP nanoparticles demonstrated good safety at a dosage of 200 mg/kg. Additionally, DSP nanoparticles demonstrated effective targeting of the liver and intestines. Therapeutic evaluation in a DSP nanoparticles-treated mouse liver hydatid model revealed that the DSP nanoparticles-H group significantly reduced liver, spleen, and vesicle weights compared to both control and albendazole (ABZ)-treated groups (P <0.05). Furthermore, the DSP nanoparticles-H group significantly decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL), and alkaline phosphatase (ALP). Additionally, levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) were significantly reduced in both serum and cystic fluid, while interferon-gamma (IFN-γ) levels were markedly increased (P <0.05). In vitro assays further demonstrated that DSP nanoparticles exert anti-echinococcal effects by compromising the integrity of the cyst wall. Mechanistic results suggest that DSP nanoparticles exert potent anti-echinococcal effects through activation of the Wnt signaling pathway and its key regulatory genes. Overall, these findings indicate that DSP nanoparticles represent a promising liver-targeted nanoformulation that not only enhances DHA bioavailability but also offers a potent therapeutic strategy against cystic echinococcosis.
Keywords: Echinococcus granulosus, Dihydroartemisinin, Sodium taurocholate, PLGA, Preparation of nanoparticles, Treatment
Received: 26 Mar 2025; Accepted: 30 May 2025.
Copyright: © 2025 Moheteer, Zhu, Pang, Rao, Aini, Aimulajiang, Zhang, Abula and Wusiman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Adelijiang Wusiman, College of Veterinary Medicine, Xinjiang Agricultural University, Ürümqi, China
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