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Preparation of Tetrandrine Nanocrystals by Microfluidic Method and Its In Vitro and In Vivo Evaluation

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Abstract

The anti-hepatocellular carcinoma effects of TET are acknowledged, but its application is hindered by its poor water solubility and low bioavailability. Conventional methods for nanocrystal preparation are laborious and lack control. To address these limitations, we propose employing the microfluidic method in the preparation of TET nanocrystals, aiming to enhance the aforementioned constraints. The objectives of this study were to prepare TET nanocrystals (TET-NC@GL) using a Y-microfluidic method with glycyrrhetinic acid (GL) as a stabilizer. The optimal preparation prescription was determined through a single-factor test and Box-Behnken response surface method. Additionally, the nanocrystals prepared with the commonly used stabilizer polyvinylpyrrolidone K30 (PVPK30), known as TET-NC@PVPK30, were characterized and evaluated for their toxicity to HepG2 cells. Hybridized nanocrystals (TET-HNC@GL and TET-HNC@PVPK30) were synthesized using a water-soluble aggregation-induced emission (AIE) fluorescent probe (TVP). Qualitative and quantitative cellular uptake experiments were conducted using these hybridized nanocrystals. Conducting in vivo pharmacokinetic assays evaluates the relative bioavailability of nanocrystals. The results indicated that TET-NC@GL, optimized using the response surface method, had a particle size of 136.47 ± 3.31 nm and a PDI of 0.219 ± 0.002. The administration of TET-NC@GL significantly enhanced the cell inhibition rate compared to the TET group and the TET-NC@PVPK30 group (P < 0.01). Moreover, the qualitative and quantitative cellular uptake results revealed a significant enhancement in cellular uptake in the TET-HNC@GL administration group compared to the TET-HNC@PVPK30 group (P < 0.01). In vivo pharmacokinetic results showed that the bioavailability of TET-NC@GL group was 3.5 times higher than that of the TET group. The results demonstrate the successful preparation of TET-NC@GL nanocrystals.

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Funding

This research was funded by Guangxi Natural Science Fundation Grant No. 2023GXNSFAA026316.

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  1. Jinping Huang and Shuwen Huang contributed equally to this work.

Authors and Affiliations

  1. Pharmaceutical College, Guangxi Medical University, Nanning, 530021, China

    Jinping Huang, Shengjun Liu, Lizhen Feng, Wenxiu Huang, Yao Wang, Dongyi Huang, Tingting Huang & Xingzhen Huang

  2. The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China

    Shuwen Huang

  3. Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Guangxi Medical University, Nanning, 530021, China

    Xingzhen Huang

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  1. Jinping Huang
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Contributions

J.H.: data management, analysis, article writing; S.H. and S.L.: nanocrystalline preparation; L.F.: nanocrystalline characterization; W.H. and Y.W.: TVP synthesis; D.H. and T.H.: review and editing; X.H.: supervision, conceptualization. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Xingzhen Huang.

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Huang, J., Huang, S., Liu, S. et al. Preparation of Tetrandrine Nanocrystals by Microfluidic Method and Its In Vitro and In Vivo Evaluation. AAPS PharmSciTech 25, 4 (2024). https://doi.org/10.1208/s12249-023-02718-1

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